Anchoring of a prosthetic valve

ABSTRACT

A prosthetic valve includes a tubular valve body, snares, and an upstream support. A native valve of a heart of a subject is disposed between an atrium and a ventricle of the heart, and has an annulus and leaflets. The prosthetic valve is advanced to the heart while in a compressed state. The prosthetic valve is positioned within the heart such that the snares are disposed upstream of the annulus and leaflets. The snares are expanded radially outwardly upstream of the leaflets. Subsequently, the prosthetic valve is moved in a downstream direction such that the snares become disposed downstream of the leaflets. While the snares remain downstream of the leaflets, the upstream support is expanded within the atrium, and the upstream support is placed against an upstream surface of the annulus. Other embodiments are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a Continuation of U.S. patent applicationSer. No. 15/703,385 to Hammer et al., filed Sep. 13, 2017, whichpublished as US 2018/0014932, and which is a Continuation of U.S. patentapplication Ser. No. 15/329,920 to Hammer et al., filed Jan. 27, 2017,which published as US 2017/0266003, and which is the US National Phaseof PCT application IL2015/050792 to Hammer et al., filed Jul. 30, 2015,and entitled “Articulatable prosthetic valve,” which published as WO2016/016899, and which claims priority from:

(i) U.S. Provisional Patent Application 62/030,715 to Hammer et al.,filed Jul. 30, 2014, and entitled “Prosthetic valve with crown”; and

(ii) U.S. Provisional Patent Application 62/139,854 to Hammer et al.,filed Mar. 30, 2015, and entitled “Prosthetic valve with crown.”

The present application is related to (i) PCT patent applicationIL2014/050087 to Hammer et al., filed Jan. 23, 2014, entitled“Ventricularly-anchored prosthetic valves”, which published as WO2014/115149, and (ii) U.S. patent application Ser. No. 14/763,004 toHammer et al., entitled “Ventricularly-anchored prosthetic valves”,which published as US 2015/0351906, and which is a US National Phase ofPCT IL2014/050087.

All of the above are incorporated herein by reference.

FIELD OF THE INVENTION

Some applications of the present invention relate in general to valvereplacement. More specifically, some applications of the presentinvention relate to prosthetic cardiac valves and techniques forimplantation thereof.

BACKGROUND

Dilation of the annulus of a heart valve, such as that caused byischemic heart disease, prevents the valve leaflets from fully coaptingwhen the valve is closed. Regurgitation of blood from the ventricle intothe atrium results in increased total stroke volume and decreasedcardiac output, and ultimate weakening of the ventricle secondary to avolume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some applications, prosthetic heart valve implants are describedthat comprise an upstream frame, a downstream frame that is distinctfrom the upstream frame, and a flexible sheet that connects and providesfluid communication between the upstream and downstream frames. For someapplications, snares are alternatively or additionally coupled to thevalve frame by a flexible sheet.

The implants described are typically secured to tissue of a native heartvalve by sandwiching the tissue between elements of the implant, such asbetween frames or frame components. The sandwiching is typicallyfacilitated by elastic coupling between the frames or frame components.The elastic coupling may be provided by the flexible sheet, or may beprovided by other means, such as by one or more of the frames, or by anadditional elastic member.

There are therefore provided, in accordance with some applications ofthe invention, the following inventive concepts:

1. Apparatus, for use with a valve of a heart of a subject, theapparatus including:

a rod, transfemorally advanceable to the heart, and having a distalportion;

an implant, including:

-   -   a first frame, compressed around a first longitudinal site of        the distal portion    -   a second frame, compressed around a third longitudinal site of        the distal portion,    -   a valve member, disposed within the second frame, and    -   a flexible sheet, coupling the first frame to the second frame,        and disposed around a second longitudinal site of the distal        portion, the second longitudinal site being between the first        longitudinal site and the third longitudinal site; and

an extracorporeal controller, coupled to a proximal portion of the rod,and operably coupled to the distal portion of the rod such thatoperating the extracorporeal controller bends the distal portion of therod at at least the second longitudinal site causing articulationbetween the first frame and the second frame.

2. The apparatus according to inventive concept 1, further including asheath, disposed over the implant, and being sufficiently flexible topassively bend in response to the bending of the rod and thearticulation between the first frame and the second frame.3. Apparatus, for use with a valve of a heart of a subject, theapparatus including:

a rod, transfemorally advanceable to the heart, and having a distalportion;

a prosthetic valve, including:

-   -   a first frame, compressed around the distal portion,    -   a second frame, compressed around the distal portion in tandem        with the first frame, and articulatably coupled to the first        frame, and    -   a valve member, disposed within the second frame; and

an extracorporeal controller, coupled to a proximal portion of the rod,and operably coupled to the distal portion of the rod such thatoperating the extracorporeal controller bends the distal portion of therod at at least the second longitudinal site causing articulationbetween the first frame and the second frame.

4. The apparatus according to inventive concept 3, further including asheath, disposed over the implant, and being sufficiently flexible topassively bend in response to the bending of the rod and thearticulation between the first frame and the second frame.5. An implant, for use with a subject, the apparatus including:

a first frame having a compressed state in which the frame istransluminally advanceable into the subject, and having a tendency toradially expand from the compressed state toward an expanded state;

a flexible sheet; and

a second frame coupled, via the flexible sheet, to the first frame, intandem with the first frame, along a longitudinal axis of the implant,

wherein the coupling of the second frame to the first frame via theflexible sheet is such that the radial expansion of the first framepulls the second frame longitudinally into the first frame by pullingthe sheet radially outward.6. An implant, for use with a subject, the apparatus including:

a first frame having a compressed state in which the frame istransluminally advanceable into the subject, and having a tendency toradially expand from the compressed state toward an expanded state; and

a second frame distinct from the first frame, and coupled to the firstframe in tandem with the first frame along a longitudinal axis of theimplant, wherein the coupling of the second frame to the first frame issuch that a radially outward force of the first frame during itsexpansion is converted into a longitudinal force that pulls the secondframe into the first frame.

7. Apparatus, including:

a delivery tool including:

-   -   a first catheter,    -   a second catheter extending through the first catheter, and    -   one or more extracorporeal controllers, coupled to a proximal        end of at least one of the first catheter and the second        catheter, and

an implant, including a first frame articulatably coupled to a secondframe, and coupled to a distal portion of the delivery tool, distal to adistal end of the first catheter and to a distal end of the secondcatheter,

wherein the one or more extracorporeal controllers are actuatable totransition the apparatus between:

a first state in which the first catheter and the second catheter arestraight, and the first frame is articulated with respect to the secondframe, and

a second state in which a distal portion of at least one of the firstcatheter and the second catheter is bent, and the first frame iscollinear with the second frame.

8. Apparatus for use with a native valve of a heart of a subject, theapparatus including:

a support frame, having a compressed state, and an expanded state inwhich the support frame defines an opening therethrough, and isdimensioned to be placed against an upstream surface of the native valvesuch that the opening is disposed over an orifice defined by the nativevalve;

a flexible sheet; and

a valve frame:

-   -   having a compressed state, and an expanded state in which the        valve frame defines a lumen therethrough,    -   including a valve member disposed within the lumen, and    -   coupled to the support frame via the flexible sheet such that        when the support frame is in its expanded state, and the valve        frame is in its expanded state, at least part of the lumen is        disposed within the opening, and the valve frame is not in        contact with the support frame.        9. The apparatus according to inventive concept 8, wherein the        apparatus is configured such that when the valve frame is in its        expanded state and the support frame is in its expanded state,        the flexible sheet extends radially outward from the valve frame        to the support frame.        10. The apparatus according to inventive concept 8, wherein the        apparatus is configured such that, when the valve frame is in        its expanded state and the support frame is in its expanded        state, the valve frame does not apply a radially-expansive force        to the support frame.        11. The apparatus according to inventive concept 8, wherein the        opening has an opening diameter, and the valve frame has a        generally tubular body that defines the lumen, and in the        expanded state of the valve frame, the tubular body has a body        diameter that is less than 75 percent as great as the opening        diameter.        12. The apparatus according to any one of inventive concepts        8-11, wherein the apparatus has a compressed state in which (i)        the support frame is in its compressed state, (ii) the valve        frame is in its compressed state, and (iii) the support frame        and the valve frame are disposed collinearly with respect to        each other, and are articulatable with respect to each other.        13. The apparatus according to inventive concept 12, wherein:

the valve frame is coupled to the support frame via a flexible sheet,and

the apparatus is configured such that:

-   -   when the valve frame is in its expanded state and the support        frame is in its expanded state, the sheet extends radially        outward from the valve frame to the support frame, and    -   when the valve frame is in its compressed state and the support        frame is in its compressed state, the support frame and the        valve frame are articulatably coupled to each other via the        sheet, and the apparatus defines an articulation zone in which        the sheet, but neither the valve frame nor the support frame, is        disposed.        14. The apparatus according to inventive concept 13, wherein:

the apparatus includes an implant including the support frame, the valveframe, and the sheet, and further includes a delivery tool, and

the apparatus has a delivery state in which (i) the support frame is inits compressed state, and is coupled to a distal portion of the deliverytool, and (ii) the valve frame is in its compressed state, and iscoupled to the distal portion of the delivery tool in tandem with thesupport frame, the apparatus is bendable at the articulation zone.

15. The apparatus according to inventive concept 14, wherein thedelivery tool includes a rod, the distal portion of the delivery tool isa distal portion of the rod, and in the delivery state, the supportframe and the valve frame both circumscribe the distal portion of therod.16. The apparatus according to inventive concept 15, wherein thedelivery tool includes an extracorporeal controller, operably coupled tothe distal portion of the rod such that in the delivery state, operatingthe extracorporeal controller bends the distal portion of the rod,causing articulation between the valve frame and the support frame.17. Apparatus including an implant, the implant being percutaneouslyimplantable, and including:

a first frame;

a second frame; and

a plurality of flexible sheets including at least a first flexible sheetand a second flexible sheet, at least the first sheet coupling the firstframe to the second frame, and the plurality of flexible sheets beingcoupled to the first frame and the second frame such that a closedchamber is disposed between the first sheet and the second sheet, and atleast one of the sheets being at least partially blood-permeable.

18. The apparatus according to inventive concept 17, wherein the chambercircumscribes at least part of the second frame, and at least part ofthe first frame circumscribes the chamber.19. The apparatus according to inventive concept 17, wherein at leastone of the sheets is configured to promote blood coagulation within thechamber.20. The apparatus according to any one of inventive concepts 17-19,wherein the second frame includes a prosthetic valve frame, dimensionedto be positioned through a native heart valve of a subject, and whereinthe first frame includes an upstream support, configured to be placedagainst an upstream surface of the heart valve.21. Apparatus including an implant, the implant being percutaneouslyimplantable, and including:

a metallic frame; and

a closed chamber:

-   -   having a toroid shape, and    -   defined by a fabric that is at least partially blood-permeable,        and is coupled to the metallic frame,        wherein the toroid shape is describable as a result of        revolving, about an axis, a cross-section of the chamber in        which:

the chamber is delimited by a boundary of the fabric, and

at least a portion of the boundary does not contact the metallic frame.

22. The apparatus according to inventive concept 21, wherein at at leastone position of the revolution, at least part of the boundary contactsthe metallic frame.23. The apparatus according to inventive concept 21, wherein at everyposition of the revolution, at least part of the boundary contacts themetallic frame.24. Apparatus for use with a native atrioventricular valve of a heart ofa subject, the apparatus including:

a prosthetic valve frame:

-   -   having an upstream end and a downstream end,    -   having a compressed state for percutaneous delivery to the        heart, and    -   being intracorporeally expandable into an expanded state thereof        in which the valve frame defines a lumen therethrough;

a plurality of prosthetic leaflets, coupled to the prosthetic valveframe so as to facilitate downstream movement of blood of the subjectthrough the lumen;

an upstream support:

-   -   having a compressed state for percutaneous delivery to the        heart, and    -   being intracorporeally expandable into an expanded state thereof        in which the upstream support is configured to be placed against        an upstream surface of the native valve, and has an inner edge        that defines an opening; and

a flexible sheet that couples the upstream support to the valve frame,the apparatus:

having a central longitudinal axis extending from an upstream end of theapparatus to a downstream end of the apparatus,

having a first state in which the valve frame is in the compressed stateof the valve frame, and the upstream support is in the compressed stateof the upstream support, and

the flexible sheet couples the valve frame to the upstream support in amanner in which movement of the apparatus toward a second state thereofpulls the valve frame longitudinally in an upstream direction such thatthe upstream end of the valve frame is disposed longitudinally upstreamof the opening.25. The apparatus according to inventive concept 24, wherein theflexible sheet couples the valve frame to the upstream support in amanner in which expansion of the upstream support toward the expandedstate thereof pulls the valve frame longitudinally in an upstreamdirection such that the upstream end of the valve frame is disposedlongitudinally upstream of the opening.26. The apparatus according to inventive concept 24, wherein in thecompressed state of the apparatus, the flexible sheet extendslongitudinally between the valve frame and the upstream support, andarticulatably couples the valve frame to the upstream support.27. The apparatus according to any one of inventive concepts 24-26,wherein in the expanded state of the apparatus, the prosthetic valveframe has a diameter that is smaller than a diameter of the opening, andthe flexible sheet is annular, and provides fluid sealing between theupstream support and the valve frame.28. The apparatus according to inventive concept 27, wherein:

the flexible sheet includes a first flexible sheet,

the apparatus further includes a second flexible sheet, and

in the expanded state of the apparatus:

-   -   the first flexible sheet extends radially inward from the        upstream support and is circumferentially attached to the valve        frame at a first longitudinal site of the valve frame, and    -   the second flexible sheet is annular, extends radially inward        from the upstream support, and is circumferentially attached to        the valve frame at a second longitudinal site of the valve frame        that is closer to the upstream end of the valve frame than is        the first longitudinal site.        29. The apparatus according to inventive concept 28, wherein the        second longitudinal site is at the upstream end of the valve        frame.        30. The apparatus according to inventive concept 28, wherein the        second longitudinal site is at least 3 mm closer to the upstream        end of the valve frame than is the first longitudinal site.        31. The apparatus according to inventive concept 28, wherein in        the expanded state of the apparatus, the apparatus defines a        chamber between the first flexible sheet and the second flexible        sheet, and the apparatus is configured to encourage tissue        growth within the chamber.        32. Apparatus, including:

a first catheter, dimensioned for transfemoral and transseptaladvancement into a left atrium of a heart of a subject, and having alumen that has an internal diameter,

a second catheter, having an external diameter that is smaller than theinternal diameter, the second catheter being sufficiently long to extendthrough the first catheter such that a steerable distal portion of thesecond catheter extends out of a distal end of the first catheter, and

a prosthetic valve, having a compressed state in which the implant istransfemorally and transseptally advanceable into the left atrium by thefirst catheter and the second catheter, and in which a width of theimplant is greater than the internal diameter.

33. Apparatus for use with a heart of a subject, the apparatusincluding:

a prosthetic valve, including a plurality of prosthetic leaflets, and aplurality of metallic struts disposed around the leaflets; and

a delivery tool,

wherein the apparatus has a delivery state in which:

the apparatus is percutaneously advanceable to the heart along alongitudinal axis of the apparatus,

a first cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, fabric, metal,and polytetrafluoroethylene (PTFE),

a second cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, fabric, andPTFE, without a metal layer between the polymer and the fabric of thesecond cross-section, or between the fabric and the PTFE of the secondcross-section, and

a third cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, pericardialtissue, metal, and PTFE,

wherein the second cross-section is disposed longitudinally between thefirst cross-section and the third cross section.34. The apparatus according to inventive concept 33, wherein the firstcross-section shows another concentric layer including fabric betweenthe layer including metal and the layer including PTFE.35. The apparatus according to inventive concept 33, wherein the thirdcross-section shows another concentric layer including fabric betweenthe layer including pericardial tissue and the layer including metal.36. The apparatus according to inventive concept 33, wherein, for eachcross-section, the layer including polymer is a component of thedelivery tool.37. The apparatus according to inventive concept 33, wherein, for eachcross-section, the layer including PTFE is a component of the deliverytool.38. The apparatus according to inventive concept 33, wherein, for eachcross-section, the layer including metal is a component of the implant.39. The apparatus according to inventive concept 33, wherein, for eachcross-section, the layer including fabric is a component of the implant.40. The apparatus according to inventive concept 33, wherein the secondcross-section shows concentric layers including, respectively, frominside outwardly: polymer, fabric, and PTFE, without struts between thepolymer and the fabric of the second cross-section, or between thefabric and the PTFE of the second cross-section.41. The apparatus according to any one of inventive concepts 33-40,wherein the second cross-section shows concentric layers including,respectively, from inside outwardly: polymer, fabric, and PTFE, withoutany metal between the polymer and the fabric of the secondcross-section, or between the fabric and the PTFE of the secondcross-section.42. Apparatus for use with a heart of a subject, the apparatusincluding:

a prosthetic valve, including a plurality of prosthetic leaflets, and aplurality of metallic struts disposed around the leaflets; and

a delivery tool,

wherein the apparatus has a delivery state in which:

the apparatus is percutaneously advanceable to the heart along alongitudinal axis of the apparatus,

a first cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, fabric, metal,and a material 100-300 microns thick,

a second cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, fabric, and thematerial 100-300 microns thick, without a metal layer between thepolymer and the fabric of the second cross-section, or between thefabric and the material 100-300 microns thick of the secondcross-section, and

a third cross-section through the apparatus shows concentric layersincluding, respectively, from inside outwardly: polymer, pericardialtissue, metal, and the material 100-300 microns thick, wherein thesecond cross-section is disposed longitudinally between the firstcross-section and the third cross section.

43. A method for use with a valve of a heart of a subject, the methodincluding:

transfemorally advancing to the heart a rod and an implant compressedaround a distal portion of the rod, the implant including a first frame,a second frame, a valve member disposed within the second frame, and aflexible sheet coupling the first frame to the second frame, wherein thefirst frame and the second frame are in tandem;

subsequently, articulating the second frame with respect to the firstframe by bending the distal portion of the rod by operating anextracorporeal controller; and

subsequently, implanting the implant at the valve such that at leastpart of the first frame is disposed on a first side of the valve and atleast part of the second frame is disposed on a second side of thevalve.

44. The method according to inventive concept 43, wherein advancing theimplant includes advancing the implant while a sheath is disposed overthe implant, and wherein the step of articulating includes articulatingthe second frame with respect to the first frame by bending the rod suchthat the sheath passively bends in response to the articulation.45. A method for use with a body of a subject, the method including:

percutaneously delivering into the body an implant in a compressedstate, the implant:

-   -   having a longitudinal axis, and    -   including a first frame, a flexible sheet, and a second frame        coupled, via the flexible sheet, to the first frame in tandem        along the longitudinal axis; and

subsequently, radially expanding the first frame such that the firstframe pulls the second frame longitudinally into the first frame bypulling the sheet radially outward.

46. A method, including:

transluminally advancing an implant to a heart of a subject while theimplant is disposed within a sheath, the implant including (i) anexpandable valve frame in a compressed state, (ii) a valve memberdisposed within the valve frame, and (iii) a plurality of snares coupledto the valve frame;

subsequently, entirely unsheathing the valve frame and the snares fromthe sheath;

subsequently, extending the snares radially outward from the valve framewhile retaining the valve frame in the compressed state; and

subsequently, expanding the valve frame radially outward.

47. A method, including:

transluminally advancing an implant to a heart of a subject, the implantincluding (i) a valve frame at a downstream portion of the implant, (ii)a valve member disposed within the valve frame, (iii) a flexible sheet,and (iv) a support frame at an upstream portion of the implant, coupledto the valve frame via the flexible sheet, wherein the valve frame andthe support frame are constrained in respective compressed states duringthe advancing; and

within the heart, (i) releasing the valve frame such that the valveframe automatically expands from its compressed state, while (ii)maintaining the support frame in its compressed state such that thesupport frame limits expansion of an upstream portion of the valve framevia tension on the sheet.

48. The method according to inventive concept 47, wherein maintainingthe support frame in its compressed state includes maintaining thesupport frame in its compressed state such that, via tension on thesheet, the support frame limits expansion of the upstream portion of thevalve frame more than expansion of a downstream portion of the valveframe.49. A method, including:

using a delivery tool, percutaneously advancing toward a heart of asubject a prosthetic valve implant coupled to a distal portion of thedelivery tool, the implant including a first frame coupled to a secondframe;

subsequently, articulating the first frame with respect to the secondframe by bending the distal portion of the delivery tool;

subsequently, reducing the articulation of the first frame with respectto the second frame by reducing the bending of the distal portion of thedelivery tool; and

subsequently, implanting the implant in the heart of the subject.

50. The method according to inventive concept 49, further including,between the step of articulating the first frame and the step ofimplanting, bending another portion of the delivery tool, the otherportion being proximal to the distal portion.51. A method for use with a mitral valve disposed between a left atriumand a left ventricle of a heart of a subject, the method including:

transfemorally and transseptally advancing an implant into the leftatrium, the implant including:

-   -   a support frame, shaped to define an opening therethrough, and    -   a valve frame, (i) coupled to the support frame via a flexible        sheet, (ii) shaped to define a lumen therethrough, and (iii)        including a plurality of prosthetic leaflets disposed within the        lumen;

placing the support frame against an upstream surface of the valve; and

placing at least part of the lumen within the opening, without placingthe valve frame in contact with the support frame.

52. The method according to inventive concept 51, wherein the placing atleast the part of the lumen within the opening includes positioning,within the opening, at least part of each leaflet of the plurality ofleaflets.53. The method according to inventive concept 51, wherein the valveframe is coupled to the support frame via a flexible sheet, and placingat least the part of the lumen within the opening includes placing atleast the part of the lumen within the opening such that the flexiblesheet extends radially outward from the valve frame to the supportframe.54. The method according to inventive concept 51, wherein the valveframe is coupled to the support frame via a flexible sheet, and placingat least the part of the lumen within the opening includeslongitudinally pulling at least the part of the lumen into the openingby tensioning the sheet by radially expanding the support frame suchthat the support frame applies tension to the sheet.55. The method according to inventive concept 51, wherein placing atleast the part of the lumen within the opening includes placing at leastthe part of the lumen within the opening such that the valve frame doesnot apply a radially-expansive force to the support frame.56. The method according to inventive concept 51, wherein the openinghas an opening diameter, a tubular body of the valve frame defines thelumen, and the method further includes expanding the tubular body suchthat the tubular body has a body diameter that is less than 75 percentas great as the opening diameter.57. The method according to any one of inventive concepts 51-56, whereinadvancing the implant includes, while the support frame is in acompressed state thereof, and the valve frame is in a compressed statethereof and is coupled to the support frame, articulating the valveframe with respect to the support frame.58. The method according to inventive concept 51, wherein advancing theimplant includes advancing the implant while the implant is in acompressed state in which the support frame and the valve frame are bothcompressed, and are coupled in tandem.59. The method according to inventive concept 58, wherein:

the valve frame is coupled to the support frame via a flexible sheetwhich provides an articulation zone between the valve frame and thesupport frame while the implant is in its compressed state, and

advancing the implant includes:

-   -   advancing the implant while the implant is (i) in its compressed        state and (ii) disposed around a rod of a delivery tool, and    -   articulating the implant at the articulation zone by operating        an extracorporeal controller to bend the rod.        60. Apparatus, including:

a sealed product container, and

an implant including a first frame, a flexible sheet, a second framecoupled to the first frame via the flexible sheet, and a valve memberdisposed within the second frame, wherein:

-   -   the implant is disposed within the sealed product container,    -   the first frame is constrained in a compressed state in which        the first frame is dimensioned for percutaneous advancement into        a subject, and    -   the second frame is in an expanded state in which the second        frame defines a lumen therethrough, the valve member is disposed        within the lumen, and the second frame is not dimensioned for        percutaneous advancement into the subject.        61. The apparatus according to inventive concept 60, further        including a crimping tool, dimensioned to receive the second        frame in the expanded state, and configured to compress the        second frame such that the second frame is dimensioned for        percutaneous advancement into the subject.        62. A method for use with an implant that includes a first frame        coupled to a second frame, and a valve member disposed within        the second frame, the method including:

while the second frame is coupled to the first frame, compressing thesecond frame into a compressed state for percutaneous advancement into asubject;

without compressing the first frame, percutaneously advancing theimplant into the subject; and

expanding the first frame and the second frame inside the subject.

63. The method according to inventive concept 62, wherein the firstframe is coupled to the second frame by a flexible sheet, and whereinexpanding the first frame and the second frame includes expanding thefirst frame and the second frame such that the expansion increasestension in the flexible sheet.64. Apparatus for use with a native valve of a heart of a subject, theapparatus including:

a valve body:

-   -   including (1) a first frame shaped to define a lumen        therethrough, and (2) a valve member disposed within the lumen,    -   having a compressed state in which the first frame has a first        diameter, and    -   having an expanded state in which the first frame has a second        diameter that is greater than the first diameter, an upstream        support:    -   configured to be placed against an upstream surface of the        native valve,    -   including a second frame,        -   having a compressed state, and        -   having an expanded state in which the second frame is            annular, has an inner perimeter that defines an opening            through the second frame, and has an outer perimeter;

one or more snares, configured to protrude radially outward from thesecond frame, and to ensnare leaflets of the native valve; and

a flexible sheet that couples the upstream support and the one or moresnares to the valve body.

65. Apparatus for use with a native valve of a heart of a subject, theapparatus including:

-   -   a valve body, shaped to define a lumen and including a valve        member disposed within the lumen, having a compressed state in        which the valve body has a first diameter, and having an        expanded state in which the first frame has a second diameter        that is greater than the first diameter,    -   a snare frame, including a plurality of snares, configured to        engage leaflets of the native valve; and    -   a flexible sheet that couples the valve body to the snare frame.        66. The apparatus according to inventive concept 65, wherein:

the apparatus includes an implant that includes the valve body, thesnare frame and the flexible sheet,

the apparatus further includes a delivery tube,

the implant has a compressed state for percutaneous delivery to thenative valve while disposed inside the delivery tube, and

in the compressed state the implant has an articulation zone, betweenthe valve body and the snare frame, in which the flexible sheet isdisposed, and at which the snare frame is articulatable with respect tothe valve body.

67. The apparatus according to inventive concept 66, wherein in thecompressed state the snares are disposed further from the valve bodythan is the articulation zone.68. The apparatus according to any one of inventive concepts 66-67,wherein the snare frame is deployable from the delivery tube while thevalve body remains disposed within the delivery tube, and the couplingof the snare frame to the valve body by the flexible sheet facilitatesexpansion of the snare frame into an expanded state thereof while thevalve body remains compressed within the delivery tube.69. The apparatus according to inventive concept 68, wherein the implantis configured such that, while the snare frame is in the expanded statethereof, expansion of the valve body into an expanded state thereofincreases a rigidity of coupling between the valve body and the snareframe.70. The apparatus according to inventive concept 68, wherein:

in the compressed state the snares are disposed closer to a downstreamend of the implant than is the articulation zone, and

the snare frame is configured such that upon deployment of the snareframe from the delivery tube, the snare frame automatically inverts suchthat the snares become disposed further from the downstream end of theimplant than is the articulation zone.

71. Apparatus for use at a native valve of a heart of a subject, theapparatus including an implant, the implant:

including an upstream frame; a downstream frame; a valve frame thatdefines a lumen; and a one-way valve member disposed within the lumen,

having an expanded state in which the one-way valve member facilitatesone-way movement of fluid through the lumen, and

having a compressed state in which the valve frame is disposedcollinearly between the upstream frame and the downstream frame, and isarticulatably coupled to both the upstream frame and the downstreamframe.

72. The apparatus according to inventive concept 71, wherein in thecompressed state:

the upstream frame defines a first rigid segment,

the valve frame defines a second rigid segment,

the downstream frame defines a third rigid segment, and

the implant defines:

-   -   a first articulation zone longitudinally separating the first        rigid segment from the second rigid segment by at least 1.5 mm,        and    -   a second articulation zone longitudinally separating the second        rigid segment from the third rigid by at least 1.5 mm.        73. The apparatus according to inventive concept 71, wherein in        the compressed state of the implant, no individual rigid segment        has a length that is greater than 22 mm.        74. The apparatus according to inventive concept 71, wherein the        implant, in its compressed state, has a length of at least 30        mm.        75. The apparatus according to inventive concept 71, wherein, in        the compressed state of the implant, a sum of (i) a length of        the first rigid segment, (ii) a length of the second rigid        segment, and (iii) a length of the third rigid segment, is at        least 35 mm.        76. The apparatus according to any one of inventive concepts        71-75, wherein the valve frame is articulatably coupled to both        the upstream frame and the downstream frame by a flexible sheet.        77. The apparatus according to inventive concept 76, wherein the        sheet provides fluid sealing between the upstream frame and the        valve frame.        78. The apparatus according to inventive concept 77, wherein the        sheet provides fluid sealing between the valve frame and the        downstream frame.        79. The apparatus according to any one of inventive concepts        71-75, further including a delivery tool, reversibly couplable        to the implant, and configured to advance the implant to the        heart while the implant is in its compressed state.        80. The apparatus according to inventive concept 79, wherein        while the implant is in its compressed state, and is coupled to        the delivery tool, the downstream frame is disposed distally to        the valve frame, and the upstream frame is disposed proximally        to the valve frame.        81. The apparatus according to any one of inventive concepts        71-75, further including a catheter, transluminally advanceable        to the heart, and through which the implant, in its compressed        state, is advanceable to the heart.        82. The apparatus according to inventive concept 81, wherein the        catheter is capable of forming a bend having a radius of        curvature of less than 13 mm, and the implant, in its compressed        state, is advanceable through the bend.        83. The apparatus according to inventive concept 81, wherein:

the catheter has an internal diameter through which the implant, in itscompressed state, is advanceable to the heart, and

in its compressed state, the implant has a length of at least 25 mm, anda greatest width that is at least 75 percent of the internal diameter ofthe catheter.

84. A method for use with a valve of a heart of a subject, the methodincluding:

providing an implant that includes:

-   -   a valve frame having an expanded state in which the valve frame        is generally cylindrical, has a central longitudinal axis, and        defines a lumen along the axis;    -   a plurality of leaflets disposed within the lumen, and    -   a plurality of snares coupled to the valve frame;

percutaneously delivering the implant through a catheter to the heartwhile the valve frame is in a compressed state;

while at least a portion of the valve frame remains disposed within thecatheter, deploying the snares from a distal end of the catheter suchthat the snares protrude radially outward and form (i) a first anglewith the axis, and (ii) a second angle with the valve frame;

subsequently, engaging tissue of the native valve using the snares; and

subsequently, by deploying more of the valve frame from the catheter,reducing the second angle by at least 50 percent, while not changing thefirst angle by more than 10 percent.

85. Apparatus, including:

a percutaneously-advanceable delivery tube; and

an implant, having a compressed state in which the implant isadvanceable through the delivery tube, and including:

-   -   a valve frame having (i) a compressed state in which the valve        frame is advanceable through the delivery tube, and (ii) an        expanded state in which the valve frame is generally cylindrical        and has a central longitudinal axis, and defines a lumen along        the axis,    -   a plurality of leaflets disposed within the lumen, and    -   a snare frame:        -   shaped to define a plurality of snares,        -   having (i) a compressed state in which the snare frame is            advanceable through the delivery tube, and (ii) an expanded            state in which the snares protrude radially outward, and        -   coupled to the valve frame such that a first angle between            the snares and the axis is independent of a second angle            between the snares and the valve frame.            86. A method, including:

providing (i) an implant that includes a first frame, a second frame,and an elastic coupling between the first frame and the second frame,and (ii) a transluminally-advanceable delivery tool;

coupling the second frame to the delivery tool by compressing the secondframe against the delivery tool;

stretching the elastic coupling by increasing a distance between thefirst frame and the second frame subsequently to coupling the secondframe to the delivery tool.

87. The method according to inventive concept 86, wherein increasing thedistance includes increasing the distance using the delivery tool.88. The method according to inventive concept 86, further includingcoupling the first frame to the delivery tool by compressing the firstframe against the delivery tool.89. The method according to any one of inventive concepts 86-88, furtherincluding transluminally advancing the implant through a catheter, whilethe implant is coupled to the delivery tool.90. The method according to inventive concept 89, wherein transluminallyadvancing the implant includes transluminally advancing the implantsubsequently to the step of stretching.91. The method according to inventive concept 89, wherein transluminallyadvancing the implant includes transluminally advancing the implantprior to the step of stretching.92. The method according to any one of inventive concepts 86-88, whereinthe first frame is coupled to a first connector of the delivery tool,and coupling the second frame to the delivery tool includes coupling thesecond frame to a second connector of the delivery tool.93. The method according to inventive concept 92, further includingcoupling the first frame to the first connector by compressing the firstframe against the delivery tool.94. The method according to inventive concept 92, wherein increasing thedistance includes increasing the distance by increasing a distancebetween the first connector of the delivery tool and the secondconnector of the delivery tool.95. Apparatus including a frame, the frame including:

a first plurality of struts, arranged to define a first annular portion;

a second plurality of struts, narrower and more flexible than the firstplurality of struts, arranged to define a second annular portion, thesecond annular portion being coupled to the first annular portion at aperimeter of the frame, such that in an unconstrained state of theframe, an angle is defined between the first annular portion and thesecond annular portion;

the frame being configured such that (i) the angle is reducible byapplying a deforming force to the frame, and (ii) the angleautomatically increases upon subsequent removal of the deforming force.

96. The apparatus according to inventive concept 95, wherein the firstannular portion defines a flexible sector that is more flexible thanother portions of the first annular portion.97. The apparatus according to inventive concept 95, wherein each strutof the first plurality of struts has a transverse cross-sectional areaof 0.25-1 mm{circumflex over ( )}2, and each strut of the secondplurality of struts has a transverse cross-sectional area of 0.04-0.2mm{circumflex over ( )}2.98. The apparatus according to inventive concept 95, wherein theperimeter of the frame defines a frame diameter of 50-70 mm.99. The apparatus according to inventive concept 95, wherein in theunconstrained state of the frame, the angle is 45-90 degrees.100. The apparatus according to any one of inventive concepts 95-99,wherein the first plurality of struts are arranged in acircumferentially-repeating chevron pattern.101. The apparatus according to inventive concept 100, wherein thesecond plurality of struts are arranged in a circumferentially-repeatingchevron pattern.102. The apparatus according to inventive concept 100, wherein thesecond plurality of struts are individual rods that protrude radiallyinward from the perimeter of the frame.103. Apparatus for use with a native atrioventricular valve of a heartof a subject, the apparatus including:

a prosthetic valve frame having an upstream end and a downstream end,and defining a lumen therebetween;

a plurality of prosthetic leaflets, coupled to the prosthetic valveframe so as to facilitate downstream movement of blood of the subjectthrough the lumen; and

an upstream support:

-   -   having an upper annular portion, and a lower annular portion        circumferentially coupled to the upper annular portion, and    -   coupled to the prosthetic valve frame such that:        -   the upper annular portion extends radially outward from a            first longitudinal site of the prosthetic valve frame toward            a perimeter of the upstream support, and        -   the lower annular portion extends radially inward from the            upper annular portion toward a second longitudinal site of            the prosthetic valve frame, the second longitudinal site            being downstream of the first longitudinal site.            104. The apparatus according to inventive concept 103,            wherein the upper annular portion extends, from the first            longitudinal site, radially outward in a downstream            direction.            105. The apparatus according to inventive concept 103,            wherein the lower annular portion extends, from the upper            annular portion, radially inward in a downstream direction.            106. The apparatus according to inventive concept 103,            wherein the lower annular portion does not contact the valve            frame.            107. The apparatus according to inventive concept 103,            wherein the lower annular portion is more flexible that the            upper annular portion.            108. The apparatus according to any one of inventive            concepts 103-107, wherein the lower annular portion is            articulatably coupled to the upper annular portion.            109. Apparatus for use with a native valve of a heart of a            subject, the apparatus including:

a prosthetic valve, shaped to define a lumen therethrough, andconfigured to be placed at the native valve, and

a prosthetic valve support:

-   -   having a generally toroid shape that has an axis of revolution,    -   configured to be placed against an annulus of the native valve,        and    -   configured, and coupled to the prosthetic valve, such that:        -   in response to tension applied to the prosthetic valve by            moving the prosthetic valve support away from the prosthetic            valve, the prosthetic valve support moves into a constrained            state by rolling about the axis of revolution in a first            direction, and        -   in response to removal of the tension, the prosthetic valve            support moves away from the constrained state by rolling            about the axis of revolution in a second direction that is            opposite to the first direction.            110. The apparatus according to inventive concept 109,            wherein the toroid shape of the prosthetic valve support            defines an opening through the prosthetic valve support, and            in a relaxed state of the apparatus, at least part of the            lumen is disposed within the opening.            111. The apparatus according to inventive concept 109,            wherein the prosthetic valve support defines at least one            ring, and is configured such that (i) a diameter of the ring            is reduced as the frame rolls in the first direction,            and (ii) the diameter of the ring is increased as the frame            rolls in the second direction.            112. The apparatus according to any one of inventive            concepts 109-111, wherein the axis of revolution            circumscribes a central longitudinal axis of the support            frame, and the generally toroid shape is describable as a            result of moving a U-shape along the axis of revolution.            113. A method for use with a valve of a heart of a subject,            the method including:

transluminally advancing an implant to the heart, the implant including:

-   -   a support frame having a generally toroidal shape, the toroidal        shape being describable as a result of moving revolving a plane        geometric figure along an axis of revolution that circumscribes        a central longitudinal axis of the support frame,    -   a valve frame, shaped to define a lumen therethrough, and        including a plurality of prosthetic leaflets disposed within the        lumen, and    -   a flexible sheet that couples the support frame to the valve        frame;

placing the support frame against an upstream surface of the valve suchthat the support frame circumscribes an orifice defined by the valve;and

causing the support frame to move the valve frame in an upstreamdirection by releasing the valve frame such that the support frame rollsabout the axis of revolution.

114. Apparatus for use with a heart of a subject, the apparatusincluding:

a prosthetic valve frame:

-   -   having an upstream end and a downstream end,    -   having a compressed state for percutaneous delivery to the        heart,    -   being intracorporeally expandable into an expanded state, and    -   defining a lumen therethrough;

a plurality of prosthetic leaflets, coupled to the prosthetic valveframe so as to facilitate one-way downstream movement of blood of thesubject through the lumen;

a support frame:

-   -   having a compressed state for percutaneous delivery to the        heart,    -   being intracorporeally expandable into a generally toroid shape        dimensioned to be placed against an upstream surface of a valve        of the heart such that the support frame circumscribes an        orifice defined by the valve, the toroid shape (i) being        describable as a result of revolving a plane geometric figure        about a central longitudinal axis of the support frame, and (ii)        defining an opening through the support frame, and    -   in the toroid shape:        -   having a first state in which the plane geometrical figure            is in a first orientation with respect to the opening,        -   being movable by a force into a constrained state in which            the plane geometrical figure is in a second orientation with            respect to the opening, and        -   being configured to automatically move from the constrained            state toward the first state upon removal of the force; and

a flexible sheet, coupling the support frame to the prosthetic valveframe, and coupled to the support frame such that the force isapplicable to the support frame by tensioning the sheet.

115. The apparatus according to inventive concept 114, wherein theflexible sheet is shaped to define a channel between the opening and thelumen.116. Apparatus for use with a native valve of a heart of a subject, theapparatus including:

a prosthetic valve frame:

-   -   having an upstream end and a downstream end,    -   having a compressed state for percutaneous delivery to the        heart,    -   being configured to be delivered to the native valve such that        at least the downstream end is disposed in a ventricle        downstream of the valve,    -   being intracorporeally expandable into an expanded state, and    -   defining a lumen therethrough;

a plurality of prosthetic leaflets, coupled to the prosthetic valveframe so as to facilitate one-way downstream movement of blood of thesubject through the lumen; and

a support frame:

-   -   having a compressed state for percutaneous delivery to the        heart,    -   being intracorporeally expandable into a generally toroid shape        that defines an opening and is dimensioned to be placed against        an upstream surface of the valve, with the opening over an        orifice defined by the valve,    -   coupled to the prosthetic valve frame, and configured such that:    -   while (i) the support frame is in the generally toroid shape and        is disposed against the upstream surface of the valve, and (ii)        at least the downstream end of the prosthetic valve frame is        disposed in the ventricle, in response to a force applied to the        support frame by downstream movement of the prosthetic valve        frame, the support frame moves into a constrained state by        rolling inward toward the orifice, and    -   in response to releasing the force, the support frame        automatically moves away from the constrained state by rolling        outward away from the orifice.        117. The apparatus according to inventive concept 116, wherein        the support frame is coupled to the prosthetic valve frame such        that there is fluid communication between the opening and the        lumen.        118. Apparatus for use at a native valve of a heart of a        subject, the apparatus including:

an upstream frame:

-   -   having a generally toroid shape,    -   having an upstream end, a downstream end, and a mid portion        therebetween,    -   being wider at the mid portion than at the upstream end or the        downstream end, and    -   defining an opening at the downstream end;

a downstream frame, distinct from the upstream frame, and defining alumen therethrough;

a flexible sheet, shaped to define a conduit, and coupled to theupstream frame and the downstream frame in a manner that provides closedfluid communication between the opening and the lumen; and

a plurality of prosthetic leaflets, configured to facilitate downstreammovement of liquid through the conduit, and to inhibit upstream movementof liquid through the conduit.

119. The apparatus according to inventive concept 118, wherein thetoroid shape is wider at the mid portion than at the upstream end, bothwith respect to an outer surface of the upstream frame, and with respectto an inner surface of the upstream frame.120. The apparatus according to inventive concept 118, wherein theopening has a diameter that is greater than a diameter of the lumen.121. The apparatus according to inventive concept 118, wherein eachprosthetic leaflet of the plurality of prosthetic leaflets has animmobilized edge attached to the flexible sheet.122. The apparatus according to any one of inventive concepts 118-121,wherein an upstream portion of the conduit is wider than a downstreamportion of the conduit.123. The apparatus according to inventive concept 122, wherein the sheetassumes a frustoconical shape.124. The apparatus according to any one of inventive concepts 118-121,wherein the prosthetic leaflets are attached to at least one elementselected from the group consisting of: the flexible sheet, and thedownstream frame.125. The apparatus according to inventive concept 124, wherein theprosthetic leaflets are attached to the flexible sheet.126. The apparatus according to inventive concept 124, wherein theprosthetic leaflets are attached to the downstream frame.127. The apparatus according to inventive concept 124, wherein theopening has a diameter that is greater than a diameter of the lumen.128. The apparatus according to any one of inventive concepts 118-121,wherein the flexible sheet facilitates intracardiac positioning of thedownstream frame at least in part independently of intracardiacplacement of the upstream frame.129. The apparatus according to inventive concept 128, wherein theupstream frame has a central longitudinal axis and the downstream framehas a central longitudinal axis, and wherein flexible sheet facilitateslateral movement of the central longitudinal axis of the downstreamframe with respect to the central longitudinal axis of the upstreamframe.130. The apparatus according to inventive concept 128, wherein theupstream frame has a central longitudinal axis and the downstream framehas a central longitudinal axis, and wherein flexible sheet facilitatesdeflection of the central longitudinal axis of the upstream frame withrespect to the central longitudinal axis of the downstream frame.131. The apparatus according to any one of inventive concepts 118-121,wherein the upstream frame is shaped and dimensioned to be placed in anatrium of the heart that is upstream of the native valve, with thedownstream end of the upstream frame disposed against an annulus of thenative valve.132. The apparatus according to inventive concept 131, wherein thedownstream frame is shaped and dimensioned to be placed in a ventricleof the heart that is downstream of the native valve.133. The apparatus according to inventive concept 132, wherein thedownstream frame is shaped and dimensioned to be placed in the ventriclewith an upstream portion of the downstream frame disposed against tissueof the native valve.134. The apparatus according to inventive concept 131, wherein theupstream frame is shaped and dimensioned to be placed in the atrium withthe downstream end of the upstream frame disposed against an annulus ofthe native valve, and the upstream end of the upstream frame not incontact with a roof of the atrium.135. The apparatus according to inventive concept 131, wherein theupstream frame has a height between the upstream end and the downstreamend, and the height of the upstream frame is smaller than a height ofthe atrium between the annulus and a roof of the atrium.136. The apparatus according to any one of inventive concepts 118-121,wherein the apparatus has:

a compressed delivery state in which the apparatus is percutaneouslydeliverable to the heart, and

an expanded state in which:

-   -   the upstream frame is in an expanded state in which the upstream        frame:        -   has the generally toroid shape,        -   is wider at the mid portion than at the upstream end or the            downstream end, and        -   defines the opening at the downstream end, and    -   the downstream frame is in an expanded state thereof in which        the downstream frame defines the lumen.        137. The apparatus according to inventive concept 136, wherein        the apparatus includes an implant including the upstream frame,        the downstream frame, the flexible sheet and the prosthetic        leaflets, and further includes:

a sheath:

-   -   percutaneously-advanceable to the native valve,    -   via which the implant is percutaneously-deliverable to the        native valve in the compressed delivery state, and    -   configured to constrain at least the downstream frame in the        compressed delivery state thereof; and

a rod, configured to be disposed within the lumen, the conduit and theopening while the implant is in the compressed delivery state within thesheath, the upstream frame and the downstream frame being held immobilewith respect to the rod while in the compressed delivery state.

138. The apparatus according to inventive concept 137, wherein theimplant is configured to be advanced distally out of the sheath suchthat the upstream frame emerges from the sheath before the downstreamframe, and the implant is further configured such that the upstreamframe remains in the compressed delivery state thereof subsequently toemerging from the sheath.139. The apparatus according to inventive concept 137, further includinga plurality of control wires extending through the rod and out of therod, coupled to the upstream frame, and configured to apply a controlforce to the upstream frame.140. The apparatus according to inventive concept 139, wherein thecontrol wires are configured to apply an upstream-directed force to theupstream frame while the downstream frame is in the expanded statethereof.141. The apparatus according to any one of inventive concepts 118-121,wherein the toroid shape is describable as the result of revolving aplane geometrical figure about a central longitudinal axis of theupstream frame, and wherein the plane geometrical figure defines aconcavity that faces radially inward toward the central longitudinalaxis.142. The apparatus according to inventive concept 141, wherein the planegeometrical figure is generally U-shaped.143. The apparatus according to any one of inventive concepts 118-121,wherein the downstream frame includes a generally tubular body and aplurality of snares that protrude radially outward from the body.144. The apparatus according to inventive concept 143, wherein thesnares protrude radially outward from an upstream portion of the body.145. The apparatus according to inventive concept 143, wherein thesnares protrude radially outward from a downstream portion of the body.146. The apparatus according to any one of inventive concepts 118-121,wherein the upstream frame is elastically coupled to the downstreamframe such that, subsequent to application of a force that increases adistance between the upstream frame and the downstream frame, when theforce is removed the distance becomes reduced.147. The apparatus according to inventive concept 146, wherein theflexible sheet is elastic, and provides the elastic coupling.148. The apparatus according to inventive concept 146, further includingat least one tether attached at a first end thereof to the upstreamframe and at a second end thereof to the downstream frame.149. The apparatus according to inventive concept 148, wherein the atleast one tether is elastic, and provides the elastic coupling.150. The apparatus according to inventive concept 146, wherein theupstream frame defines at least one spring that provides the elasticcoupling.151. The apparatus according to inventive concept 150, wherein the atleast one spring is coupled to a first end of a respective tether, and asecond end of the respective tether is coupled to the downstream frame.152. The apparatus according to inventive concept 150, wherein the atleast one spring is defined by the upstream end of the upstream frame.153. The apparatus according to inventive concept 150, wherein the shapeof the sheet and the coupling of the sheet to the upstream frame and thedownstream frame positions the at least one spring with respect to thesheet such that the at least one spring provides the elastic coupling bypulling the sheet in an upstream direction.154. The apparatus according to inventive concept 150, wherein the atleast one spring is defined by the downstream end of the upstream frame.155. A method for use at a native valve of a heart of a subject, thenative valve being disposed between an atrium and a ventricle of theheart, and having an annulus and native leaflets, the method including:

positioning a distal portion of a sheath at the native valve, such thatthe native leaflets coapt against the sheath, the sheath containing, ina compressed state, an implant including an upstream frame, a downstreamframe distinct from the upstream frame, a flexible sheet that couplesthe upstream frame to the downstream frame, and a plurality ofprosthetic leaflets;

exposing a portion of the downstream frame from the sheath such that theportion of the downstream frame expands, and the native leaflets coaptagainst the portion of the downstream frame;

moving the implant downstream until the leaflets coapt upstream of theportion of the downstream frame;

applying an upstream force to the native leaflets with the downstreamframe by moving the implant upstream; and

expanding the upstream frame within the atrium.

156. The method according to inventive concept 155, wherein the portionof the downstream frame includes snares of the downstream frame, andwherein exposing the portion includes exposing the portion such that thesnares protrude radially outward.157. The method according to inventive concept 155, wherein:

the portion of the downstream frame includes snares of the downstreamframe,

exposing the portion of the downstream frame includes exposing theportion of the downstream frame such that the snares protrude radiallyoutward, and

applying the upstream force includes applying the upstream force withthe snares.

158. The method according to inventive concept 155, wherein the portionof the downstream frame includes an upstream portion of the downstreamframe, and wherein exposing the portion of the downstream frame includesexposing the upstream portion of the downstream frame.159. The method according to inventive concept 155, wherein applying theupstream force with the downstream frame includes applying the upstreamforce with the portion of the downstream frame.160. The method according to inventive concept 155, further including,subsequently to moving the step of moving the implant downstream, andprior to the step of applying the upstream force, further expanding theportion of the downstream frame by exposing more of the downstream framefrom the sheath.161. The method according to any one of inventive concepts 155-160,further including, subsequently to the step of expanding, applying acontrol force to the upstream frame.162. The method according to inventive concept 161, wherein applying thecontrol force includes applying the control force by adjusting tensionon one or more control wires reversibly coupled to the upstream frame.163. The method according to inventive concept 161, wherein applying thecontrol force includes pulling the upstream frame in an upstreamdirection.164. The method according to inventive concept 161, wherein applying thecontrol force includes pulling the upstream frame radially inward.165. The method according to any one of inventive concepts 155-160,wherein the step of exposing includes exposing the upstream frame, thenthe sheet, and then the portion of the downstream frame.166. The method according to inventive concept 165, wherein the step ofexposing includes withdrawing the sheath proximally.167. The method according to any one of inventive concepts 155-160,further including, subsequently to the step of applying the upstreamforce to the native leaflets, sandwiching tissue of the native valvebetween the upstream frame and the downstream frame by reducing adistance between the upstream frame and the downstream frame by removinga separating force that maintains a distance between the upstream frameand the downstream frame.168. The method according to inventive concept 167, further including,prior to removing the separating force, increasing the distance betweenthe upstream frame and the downstream frame by applying the separatingforce to the implant.169. The method according to inventive concept 167, wherein the step ofexpanding the upstream frame includes releasing the upstream frame suchthat the upstream frame automatically expands and the separating forceis removed.170. The method according to inventive concept 167, wherein the step ofexpanding the upstream frame includes releasing a restraining elementthat maintains the upstream frame in the compressed state thereof.171. The method according to inventive concept 170, wherein releasingthe restraining element includes disengaging a retaining member from therestraining element.172. The method according to inventive concept 171, further includingwithdrawing the retaining member alongside the implant, and withdrawingthe restraining element via the lumen.173. The method according to any one of inventive concepts 155-160,further including, using imaging, observing coaptation of the nativeleaflets and the implant juxtaposed with respect to the native leaflets,and wherein the step of positioning includes observing the upstreamframe disposed upstream of a level of coaptation of the native leaflets.174. The method according to inventive concept 173, wherein observingthe implant in a position in which the upstream frame is disposedupstream of a level of coaptation of the native leaflets includesobserving the portion of the downstream frame disposed at the level ofcoaptation of the native leaflets.175. The method according to inventive concept 173, wherein observingthe implant in a position in which the upstream frame is disposedupstream of a level of coaptation of the native leaflets includesobserving the sheet disposed upstream of a level of coaptation of thenative leaflets and downstream of the upstream frame.176. Apparatus for use at a native valve of a heart of a subject, thenative valve being disposed between an atrium and a ventricle of theheart, and having an annulus, the apparatus including:

an upstream frame, shaped to define an opening, and configured to beplaced in the atrium against the annulus;

a downstream frame, distinct from the upstream frame, and defining alumen therethrough;

a flexible sheet, shaped to define a conduit and coupled to the upstreamframe and the downstream frame such that, in an expanded state of theapparatus, the sheet is disposed upstream of the downstream frame anddownstream of the upstream frame, and provides closed fluidcommunication between the opening and the lumen; and

a plurality of prosthetic leaflets:

-   -   each prosthetic leaflet of the plurality of leaflets having an        immobilized edge attached to the sheet, and    -   configured to facilitate downstream movement of liquid through        the conduit, and to inhibit upstream movement of liquid through        the lumen.        177. Apparatus for use at a native valve of a heart of a        subject, the native valve being disposed between an atrium and a        ventricle of the heart, and having an annulus, the apparatus        including:

at least one expandable frame, having a compressed state forpercutaneous delivery to the native valve, and intracorporeallyexpandable into an expanded state;

a flexible sheet, coupled to the at least one frame, and shaped todefine a conduit; and

a plurality of prosthetic leaflets:

-   -   configured to facilitate downstream movement of liquid through        the conduit, and to inhibit upstream movement of liquid through        the conduit, and    -   attached to the sheet and not sutured to the frame.        178. A method for use at a native valve of a heart of a subject,        the native valve being disposed between an atrium and a        ventricle of the heart, and having an annulus and native        leaflets, the method including:

percutaneously delivering an implant in a compressed state thereof tothe native valve;

positioning the implant such that:

-   -   a first frame of the implant is disposed upstream of the native        valve,    -   a second frame of the implant, distinct from the first frame and        coupled to the first frame by a flexible sheet, is disposed        downstream of the native valve, and    -   the flexible sheet traverses the native valve;

expanding at least a portion of the second frame; and

subsequently expanding the first frame.

179. The method according to inventive concept 178, wherein the step ofexpanding at least the portion of the second frame includes expanding atleast the portion of the second frame prior to the step of positioningthe implant.180. The method according to inventive concept 178, wherein the step ofexpanding at least the portion of the second frame includes expanding atleast the portion of the second frame subsequently to the step ofpositioning the implant.181. The method according to any one of inventive concepts 178-180,wherein the portion of the second frame includes one or more snares ofthe second frame, and expanding at least the portion of the second frameincludes expanding at least the snares.182. The method according to inventive concept 181, further including,subsequently to expanding at least the snares, and prior to expandingthe first frame, moving the implant upstream such that the snares applyan upstream force to tissue of the native valve.183. The method according to any one of inventive concepts 178-180,further including sandwiching of the native leaflets between the firstframe and the second frame by facilitating reduction of a distancebetween the first frame and the second frame.184. The method according to inventive concept 183, wherein the secondframe is elastically-coupled to the first frame, and facilitatingreduction of the distance includes allowing the elastic coupling toreduce the distance.185. A method for use at a native valve of a heart of a subject, thenative valve being disposed between an atrium and a ventricle of theheart, and having an annulus and native leaflets, the method including:

percutaneously delivering to the native valve an implant having anupstream end, a downstream end, and a longitudinal axis therebetween;

subsequently, expanding a longitudinal portion of the implant that doesnot include the upstream end or the downstream end; and

subsequently, expanding the upstream end and the downstream end.

186. The method according to inventive concept 185, wherein the step ofexpanding the upstream end and the downstream end includes expanding thedownstream end and subsequently expanding the upstream end.187. The method according to any one of inventive concepts 185-186,wherein:

the implant includes an upstream frame, a downstream frame, and aflexible sheet that couples and provides fluid communication between theupstream frame and the downstream frame,

the longitudinal portion includes an upstream portion of the downstreamframe and a downstream portion of the sheet, and

expanding the longitudinal portion includes expanding the upstreamportion of the downstream frame and the downstream portion of the sheet.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-C and 2 are schematic illustrations of an implant comprising anupstream frame, a downstream frame that is distinct from the upstreamframe, and a flexible sheet connecting the upstream and downstreamframes, in accordance with some applications of the invention;

FIGS. 3A-C are schematic illustrations of respective placements of theimplant at a native mitral valve of a subject, in accordance with someapplications of the invention;

FIGS. 4A-J are schematic illustrations of delivery and implantation ofthe implant, in accordance with some applications of the invention;

FIGS. 5-8 are schematic illustrations of respective implants eachcomprising an upstream frame elastically coupled to a downstream frameand a flexible sheet that provides fluid communication between the twoframes, in accordance with some applications of the invention; and

FIGS. 9-10 are schematic illustrations of implants having atraumaticmodifications, in accordance with some applications of the invention;

FIG. 11 is a schematic illustration of an implant, in accordance withsome applications of the invention;

FIGS. 12A-C are schematic illustrations of delivery and implantation ofan implant, in accordance with some applications of the invention;

FIGS. 13A-C and 14A-C are schematic illustrations of implants that eachcomprise an upstream frame, a downstream frame, and a flexible sheetconnecting the upstream and downstream frames, in accordance with someapplications of the invention;

FIGS. 15A-C, 16A-D, and 17 are schematic illustrations of an implant,and implantation thereof, in accordance with some applications of theinvention;

FIGS. 18 and 19A-B are schematic illustrations of frames of upstreamsupports, in accordance with some applications of the invention;

FIGS. 20A-C are schematic illustrations of an implant comprising asupport frame, a prosthetic valve frame, and a flexible sheet couplingthe support frame to the prosthetic valve frame, in accordance with someapplications of the invention;

FIGS. 21A-C are schematic illustrations of a system for stretching anelastic coupling between frames of an implant, in accordance with someapplications of the invention; and

FIGS. 22, 23, 24A-C, and 25A-K are schematic illustrations of animplant, and a system comprising the implant and a delivery tool, inaccordance with some applications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-C and 2, which are schematic illustrationsof an implant 20 comprising an upstream frame 22, a downstream frame 24that is distinct from the upstream frame, and a flexible sheet 26connecting the upstream and downstream frames, in accordance with someapplications of the invention. FIGS. 1A-B show respective perspectiveviews of implant 20, FIG. 1C shows an end view of the implant, and FIGS.2A-B show side views of the implant. Typically upstream frame 22 anddownstream frame 24 each define (or are each defined by) a regularlytiled distribution of cells (e.g., a two-dimensional shape) thatprovides the three-dimensional shape of the frame. Alternatively, theupstream frame and/or the downstream frame may have a differentstructure, e.g., may comprise a wire frame and/or a braided mesh.

Frame 22 has a generally toroid shape, having an upstream end 32, adownstream end 34, and a mid portion 36 therebetween. Mid portion 36 hasa width d1 that is greater than a width d2 of downstream end 34 or awidth d3 of upstream end 32. That is, frame 22 is typically wider at midportion 36 than at upstream end 32 or downstream end 34. Upstream anddownstream portions of frame 22 curve radially inward to provide frame22 with this shape. It is to be noted that, although d2 and d3 are shownas being generally equal, for some applications of the invention thesewidths are different. For some applications, width d1 is greater than 35mm and/or less than 75 mm (e.g., 35-75 mm, such as 50-65 mm). For someapplications, width d2 and/or width d3 is greater than 35 mm and/or lessthan 60 mm (e.g., 35-60 mm, such as 40-50 mm). Frame 22 (e.g.,downstream end 34 thereof) defines an opening 28 therethrough.

Typically, and as shown, frame 22 is wider at mid portion 36 than atupstream end 32 or downstream end 34, both with respect to an outersurface of the upstream frame, and with respect to an inner surface ofthe upstream frame. Therefore, the inner surface of the frame typicallydefines a ring-shaped concavity 52 upstream of downstream end 34 (seeFIG. 1A). A toroid is describable as the result of revolving a planegeometrical figure about an axis. Typically, the toroid shape of frame22 is describable as the result of revolving a plane geometrical figureabout a central longitudinal axis ax1 of the upstream frame, the planegeometrical figure defining a concavity 54 that faces radially inwardtoward axis ax1. For some applications, and as shown, this planegeometric figure is generally U-shaped. Revolution of concavity 54 aboutaxis ax1 results in concavity 52.

For some applications, when viewed from the side, frame 22 appearsgenerally stadium-shaped, and/or as a rectangle with rounded corners.

It is to be noted that, in its expanded state, frame 22 defines at leasttwo layers. That is, a line parallel with and lateral to axis ax1 (i.e.,closer to the outer edge of frame 22) will pass through the frame atleast twice. For example, in the configuration of frame 22 shown in thefigures, upstream end 32 defines a first layer and downstream end 34defines a second layer. It is hypothesized that such a configurationincreases stiffness of frame 22 in its expanded state, in a mannersimilar to that of a structural channel (known in the construction art),mutatis mutandis. It is to be noted that the scope of the inventionincludes other configurations (e.g., structures) of frame 22 that defineat least two layers.

Frame 24 defines a generally tubular valve body 40 and a lumen 30therethrough. Frame 24 (e.g., body 40) has an upstream portion 42(including an upstream end) and a downstream portion 44 (including adownstream end). A plurality of snares (e.g., protrusions) 46 protruderadially outward from tubular body 40, thereby defining a diameter d11that is greater than a diameter d12 of body 40.

Typically, snares 46 protrude outward in an upstream direction (i.e.,toward upstream frame 22), e.g., at an angle alpha_1 greater than 10degrees (e.g., greater than 15 degrees, e.g., greater than 25 degrees)and/or less than 90 degrees (e.g., less than 80 degrees, e.g., less than55 degrees), such as 10-90 degrees (e.g., 15-80 degrees, e.g., 25-55degrees), such as about 40 degrees. For some applications, and as shown,snares 46 are disposed at upstream portion 42. Typically, each snare 46is defined by a cell of frame 24 that is bent out of plane to body 40.Alternatively, snares 46 may be disposed elsewhere on tubular body 40,such as at downstream portion 44 (e.g., as described hereinbelow withreference to FIGS. 8, 13A-C, 14A-C, 15A-17, and/or 20A-C, mutatismutandis).

Frame 24 (and lumen 30) has a height that is typically greater than 8 mmand/or less than 40 mm, such as between 8 and 40 mm (e.g., between 12and 25 mm, such as between 15 and 20 mm). For some applications thisheight is defined by a height of tubular body 40; this height isrepresented in FIG. 2 by reference numeral d5. For some applicationsthis height includes additional height provided by snares 46; thisheight is represented in FIG. 2 by reference numeral d5′. For someapplications, the height of frame 24 is greater than 8 mm and/or lessthan 40 mm (e.g., 8-40 mm, such as 12-25 mm).

Frames 22 and 24 are typically thin-walled (e.g., having a thickness d14(FIG. 4D) of less than 1.5 mm, greater than 0.2 mm, and/or between 0.2and 1.5 mm, e.g., 0.4-1.5 mm). Therefore diameter d2 of downstream end34 of upstream frame 22 is typically similar to the diameter of opening28, and diameter d12 of body 40 is typically similar to the diameter oflumen 30 (e.g., less than 3 mm, more than 1 mm, and/or between 1 and 3mm difference in each case).

Sheet 26 is shaped to define a conduit 48, and is coupled to frames 22and 24 in a manner that provides closed fluid communication betweenopening 28 and lumen 30. Diameter d2 is typically greater than diameterd12, and the diameter of opening 28 is typically greater than thediameter of the lumen 30. Therefore an upstream portion of conduit 48(i.e., a portion closer to upstream frame 22) is typically wider than adownstream portion of the conduit (i.e., a portion closer to downstreamframe 24). For some applications, sheet 26 assumes a frustoconical orfunnel shape, and may in fact serve as a funnel. The shape assumed bysheet 26 is typically at least partly guided by the expansion of frames22 and 24.

Sheet 26 (i.e., a material thereof) may be a fabric, a film, and/oranother sheet-like structure, and may comprise a natural material, apolymer, a biomaterial, and/or any other suitable material.

Typically, sheet 214 comprises polyester, PTFE, and/or pericardialtissue.

For some applications, sheet 26 is coupled to frame 22 at a level thatis upstream of opening 28, and for some applications the sheet iscoupled to frame 24 at a level that is downstream of upstream portion42. For example, portions of sheet 26 may line and/or cover at leastpart of (e.g., all of) frame 24, and at least part of frame 22. Forexample, and as shown, the sheet may line most of frame 22 and at leasta downstream portion of frame 22 (including downstream end 34). Theflexibility of such portions of the sheet is in effect reduced by beingattached to the respective frame.

Therefore, throughout this patent application, including thespecification and the claims, unless specified otherwise, the term“flexible sheet” refers to portions of the sheet disposed between theframes (e.g., longitudinally between the frames), and typically not toportions of the sheet that line and/or cover the frames. It is to benoted that sheet 26 is not attached to snares 46.

Implant 20 comprises a valve member (e.g., a plurality of prostheticleaflets) 50, configured to facilitate downstream movement of liquid(e.g., blood) through the apparatus (e.g., through opening 28, conduit48, and lumen 30), and to inhibit upstream movement of the liquidthrough the apparatus.

Leaflets 50 are shown in FIGS. 1B-C, but for simplicity, not in otherfigures. Typically, leaflets 50 are at least in part disposed withinlumen 30. For some applications, leaflets 50 are alternatively oradditionally at least in part disposed within conduit 48. For someapplications, at least part of each leaflet is attached (e.g., sutured)to frame 24 (i.e., at least part of an immobilized edge of each leafletis attached to frame 24).

For some applications, at least part of the immobilized edge of eachleaflet is attached (e.g., sutured) to sheet 26 (i.e., within conduit48). FIG. 1B illustrates an example in which an immobilized edge of eachleaflet is attached along an attachment line 56 that extends betweenframe 24 and sheet 26, i.e., each leaflet is attached within lumen 30and within conduit 48. Parts of the leaflet that are attached (e.g.,sutured) to sheet 26 are thus not attached (e.g., sutured) to frame 24(snares 46 are not attached to sheet 26, and extend away from thesheet). For some applications, such parts of the leaflet are notattached to a metallic structure. For some applications, a reinforcingwire 58 is provided along attachment line 56, but it is to be noted thatthe reinforcing wire is typically distinct from frame 24.

For some applications, leaflets 50 are coupled only indirectly to frame24 (e.g. by being attached to sheet 26, which is attached to the frame).Thus, for some applications, leaflets 50 are secured within implant 20only by being attached to a sheet (e.g., a fabric) that is tensidned byone or both frames.

Implant 20 is configured to be placed at a native heart valve of asubject, such as the mitral valve or tricuspid valve. Upstream frame 22is shaped and dimensioned to be placed in an atrium of the heart that isupstream of the native valve, such as the left atrium, with downstreamend 34 disposed against tissue of the native valve, such as against anannulus of the native valve. Typically, frame 22 is shaped anddimensioned to be placed in this position, with upstream end 32 not incontact with the roof of the atrium (i.e., the superior wall of theatrium). That is, frame 22 typically has a height d4 between upstreamend 32 and downstream end 34 that is smaller than the height of theatrium between the annulus and the atrial roof. For some applications,height d4 is greater than 2 mm (e.g., greater than 7 mm) and/or lessthan 30 mm, e.g., between 2 and 30 mm (e.g., between 7 and 30 mm, suchas between 10 and 20 mm). Examples of the positioning described in thisparagraph are described in more detail hereinbelow, e.g., with referenceto FIGS. 4A-J.

FIGS. 1A-2 show implant 20 in an expanded state thereof. That is, theabove description of frames 22 and 24 are descriptions of the frames inrespective expanded states. Implant 20 further has a compressed deliverystate in which upstream frame 22 and downstream frame 24 are inrespective compressed delivery states, and in which the implant ispercutaneously deliverable to the heart (e.g., as describedhereinbelow). Typically, frames 22 and 24 comprise a shape memorymaterial (e.g., nitinol), are constrained in their expanded statesduring delivery, and are configured to automatically move toward theirexpanded shapes when this constraint is removed.

Upstream frame 22 is typically elastically-coupled to downstream frame24, such that a distance between the two frames is increasable to adistance d6 by applying a force, and in response to subsequent removalof that force, the distance automatically becomes reduced to a distanced7 (see FIG. 2). The overall height of implant 20, from upstream end 32of upstream frame 22 to downstream portion 44 of downstream frame 24,changes correspondingly to the change in distance between the twoframes. Thus the state of implant 20 on the left side of FIG. 2 may beconsidered an extended state, and the state of the implant on the rightside of the figure may be considered a contracted state.

For some applications, distance d6 is greater than 0 mm and/or less than35 mm (e.g., 0-35 mm, such as 5-18 mm). For some applications, distanced7 is greater than 0 mm and/or less than 25 mm (e.g., 0-25 mm, such as0-10 mm). For some applications, in the absence of tissue disposedbetween frames 22 and 24, upstream portion 42 of frame 24 may actuallybe disposed within a space defined by frame 22 (e.g., may be disposedmore than 1 mm and/or less than 10 mm (e.g., 1-10 mm, such as 1-5 mm)upstream of opening 28 of frame 22). For such applications, thisdistance upstream may be considered a negative value of distance d7,such that, overall, distance d7 may be greater than −10 mm and/or lessthan 25 mm (e.g., between −10 and 25 mm, such as between −5 and 10 mm).

For implant 20, the elastic coupling is provided by sheet 26. Forexample, sheet 26 may be a sheet of an elastic material, and/or maycomprise one or more elastic threads embedded within, threaded through,and/or attached to the material of the sheet. For other systems similarto implant 20, other elements provide the elastic coupling, such as, butnot limited to, those described with reference to FIGS. 5-8.

Reference is made to FIGS. 3A-C, which are schematic illustrations ofrespective placements of implant 20 at a native mitral valve 10 of asubject, in accordance with some applications of the invention. Mitralvalve 10 is disposed between left atrium 6 and left ventricle 8 of thesubject, and comprises an annulus 14 that supports native valve leaflets12. As described hereinabove, upstream frame 22 is shaped anddimensioned to be placed in atrium 6, typically with downstream end 34of the frame disposed against tissue of the native valve, such asagainst an annulus 14. Typically, in this position, upstream end 32 isnot in contact with the roof of the atrium (not shown). That is, heightd4 of frame 22 is typically smaller than a height d8 of the atriumbetween the annulus and the atrial roof.

For some applications, upstream frame 22 is shaped and dimensioned to beplaced such that downstream end 34 is disposed above (i.e., upstream of)the native annulus. Typically, upstream frame 22 is dimensioned suchthat, when implanted, any covered and/or lined portion of upstream frame22 is disposed below a level of the pulmonary vein ostia (i.e.,downstream of the ostia) so as not to obstruct blood flow therethrough.For applications in which frame 22 is entirely lined and/or coated,height d4 is less than a height between the valve annulus and thepulmonary vein ostia. For applications in which frame 22 is not entirelylined and/or coated (e.g., the frame is not lined or coated, and/or onlya downstream portion of the frame is lined and/or coated), the frame isdimensioned such that at least the lined and/or coated portions of theframe are disposed below the level of the pulmonary vein ostia (whereasuncovered and/or unlined portions of the frame may be disposed at thepulmonary vein ostia).

Downstream frame 24 is shaped and dimensioned to be placed in ventricle8, typically with upstream portion 42 and/or snares 46 in contact withtissue of the mitral valve, such as leaflets 12.

As described hereinbelow (e.g., with reference to FIGS. 4A-J), implant20 is secured in place by utilizing the elastic coupling of upstreamframe 22 downstream frame 24 to sandwich tissue of the native valvebetween upstream frame 22 and downstream frame 24 (e.g., snares 46).That is, the elastic coupling provides a sandwiching force whichsandwiches the tissue between frames 22 and 24 by drawing the framescloser together along an upstream-downstream axis.

It is to be noted that throughout this application, including thespecification and the claims, sandwiching of tissue between apparatuscomponents means reducing a distance between the components while thetissue is disposed between the components (thereby typically increasingcoupling to the tissue). Sandwiching does not necessarily require thatthe components move directly toward each other (e.g., having oppositebut collinear vectors). For example, for applications in which diameterd11 is equal to or slightly larger than diameter d12, sandwiching may infact occur as a result of snares 46 and downstream end 34 of frame 22moving directly toward each other. However, for applications in whichdiameter d1 is smaller than diameter d12 (as shown), snares 46 and end34 may not move directly toward each other, but may instead move asthough they would eventually pass each other, nonetheless reducing thedistance between these two components.

Inter alia, FIGS. 3A-C illustrate that sheet 26 facilitates intracardiacpositioning of downstream frame 24 at least in part independently ofintracardiac placement of upstream frame 22.

FIG. 3A shows implant 20 having been implanted at mitral valve 10 withaxis ax1 of upstream frame 22 collinear with a central longitudinal axisax2 of downstream frame 24 (e.g., in a theoretical perfectly symmetricalmitral valve). FIG. 3B shows implant 20 having been implanted at themitral valve with axis ax1 disposed at a nonzero angle alpha_2 (e.g.,deflected) with respect to axis ax2.

Sheet 26 (e.g., the flexibility thereof) facilitates such deflection ofaxis ax1 with respect to axis ax2 while maintaining fluid communicationbetween frames 22 and 24. FIG. 3C shows implant 20 having been implantedat the mitral valve with axis ax1 laterally offset (e.g., translated)with respect to axis ax2. Sheet 26 (e.g., the flexibility thereof)facilitates such lateral movement of axis ax1 with respect to axis ax2while maintaining fluid communication between frames 22 and 24. It ishypothesized that implant 20 is thereby adaptable to variousimplantation conditions, such as to anatomical dimensions, whilemaintaining one-way fluid communication between the atrium andventricle.

Reference is now made to FIGS. 4A-J, which are schematic illustrationsof delivery and implantation of implant 20, in accordance with someapplications of the invention. FIGS. 4A-J show transapical delivery andimplantation of implant 20, but it is to be noted that the scope of theinvention includes transatrial, transfemoral and/or transseptal deliveryof the implant, mulatis mutandis.

A trocar 60 is transapically (e.g., intercostally) advanced intoventricle 8, and implant 20, in its compressed delivery state within asheath 62, is delivered via the trocar (FIG. 4A). In the compresseddelivery state of implant 20, frames 22 and 24 are in tandem (i.e., oneafter the other), coupled via sheet 26. Typically, the distal end ofsheath 62 is advanced into atrium 6, and implant 20 is positioned suchthat upstream portion 42 of downstream frame 24 is disposed at the levelof coaptation of leaflets 12, or further into the atrium (i.e., furtherupstream). Sheath 62 and sheet 26 are typically radiotransparentrelative to frames 22 and 24, and the operating physician is typicallyable to identify this positioning using ultrasound and/or fluoroscopy.In this position leaflets 12 coapt against sheath 62. (That is, centralportions (e.g., the a2 and p2 scallops) of the leaflets coapt againstthe sheath, while portions of the leaflets closer to the commissures(e.g., the a1, a3, p1, and p3 scallops) may coapt against each other.)

Sheath 62 is subsequently partially withdrawn (i.e., moved downstream)such that upstream frame 22, sheet 26, and at least upstream portion 42and/or snares 46 of downstream frame 24 are exposed from the sheath(FIG. 4B). Although upstream frame 22 emerges from sheath 62 beforedownstream frame 24, upstream portion 42 of downstream frame 24automatically expands toward its expanded state, whereas upstream frame22 is maintained in its compressed delivery state by at least onerestraining element 64, such as a restraining filament (described inmore detail hereinbelow).

Typically, upstream portion 42 expands to greater than 50 percent of itsfully expanded diameter (e.g., greater than 50 percent and/or less than80 percent, such as 50-80 percent, e.g., 60-80%). Following withdrawalof sheath 62, leaflets 12 coapt against implant 20 itself.

Due to the above-described position of implant 20, the leaflets coaptagainst upstream portion 42, and because of the expansion of thisportion, during ventricular systole, a distance d9 between the leafletsat the point of this coaptation (e.g., between scallops a2 and p2) isgreater than the distance when they previously coapted against sheath62. This increased distance is observable by the operating physicianusing imaging techniques, e.g., as described hereinabove. For someapplications, distance d9 is greater than 8 mm and/or less than 18 mm(e.g., 8-18 mm, such as 10-15 mm).

Subsequently, implant 20 and sheath 62 are withdrawn slightly proximally(i.e., downstream), until leaflets 12 coapt above upstream portion 42and/or snares 46 (e.g., against sheet 26 and/or upstream frame 22).Because frame 22 has not expanded, a distance d10 between the leafletsduring systole is now smaller than distance d9. This reduced distance isobservable by the operating physician using imaging techniques, e.g., asdescribed hereinabove. For some applications, distance d10 is greaterthan 5 mm and/or less than 12 mm (e.g., 5-12 mm, such as 6-8 mm).Typically, the withdrawal of implant 20 and sheath 62 is performedslowly, while observing leaflets 12, and withdrawal is stopped as soonas the physician observes a reduction in the systolic distance betweenthem. It is hypothesized that this facilitates identification of aposition of implant 20 in which upstream portion 42 of downstream frame24 is close to, but downstream of, the level of coaptation of leaflets12.

For some applications, at this stage, sheath 62 is further withdrawnwith respect to implant 20, exposing more of downstream frame 24 (e.g.,including some of downstream portion 44 thereof), and therebyfacilitating further automatic expansion of the downstream frame (FIG.4D). For example, upstream portion 42 may expand to greater than 70percent of its fully expanded diameter (e.g., greater than 80 percent,such as greater than 90 percent, e.g., about 100 percent).Alternatively, this further withdrawal of sheath 62 and expansion ofdownstream frame 24 may be omitted.

It is to be noted that, for some applications, a longitudinal portion ofimplant 20 other than an end of the implant (e.g., a generally middleportion of the implant—upstream portion 42 and/or snares 46) is expandedprior to expansion of either end of the implant.

Typically, movement of downstream frame 24 with respect to sheath 62 iscontrolled via a mount 72, which is slidable though the sheath. Mount 72comprises a body portion 76, and one or more flanges 74 via which it isreversibly coupled to frame 24. Mount 72 is dimensioned such that, whileflanges 74 are disposed close to (e.g., touching) the inner wall ofsheath 62, a gap 78 having a width d13 exists between body portion 76and the inner wall of the sheath. Width d13 is greater than thicknessd14 of frame 24, e.g., more than twice as great and/or less than 20times as great, e.g., 2-20 times as great, such as 2-6 times as great.Thus, flanges 74 typically protrude radially outward from body portion76 by a distance that is greater than thickness d14 (e.g., more thantwice as great and/or less than 20 times as great, e.g., 2-20 times asgreat, such as 2-6 times as great).

Frame 24 is thereby movable radially inward and outward within gap 78,such that when the upstream part of the frame expands radially outward,the downstream end of the frame moves radially inward, frame 24 therebypivoting about flanges 74. It is hypothesized that this configurationthereby proximal portion 42 and/or snares 46 of frame 24 expandingradially outward further than they would in a similar configuration inwhich width d13 is generally the same as thickness d14, i.e., in aconfiguration in which frame 24 fits snugly between body portion 76 andsheath 62.

Implant 20 and sheath 62 are subsequently moved distally (i.e.,upstream), such that upstream portion 42 and/or snares 46 contact andapply an upstream force to tissue of the native valve, such as leaflets12 (FIG. 4E). Because of the technique described hereinabove in which,prior to the step shown in FIG. 4E, upstream portion 42 is close to thelevel of coaptation of the leaflets, the distance that snares 46 travelupstream during the step shown in FIG. 4E is reduced (e.g., minimized),thereby reducing a probability that the snares might engage and/ordamage other anatomical structures, such as chordae tendineae orventricular walls.

Subsequently, sheath 62 is withdrawn further thereby exposing downstreamportion 44 of downstream frame 24, and frame 24 automatically expandsfully into its expanded state (FIG. 4F), typically becoming decoupledfrom mount 72 (described with reference to FIG. 4D).

Upstream frame 22 is subsequently allowed to expand by releasingrestraining element 64 while maintaining contact between upstreamportion 42 (and/or snares 46) and the tissue of the native valve (FIG.4G). As shown, restraining element 64 may comprise a single filamentwrapped around frame 22 (e.g., wrapped several times around the frame).Alternatively, more than one restraining element may be used. For someapplications, restraining element 64 may be held in place by a retainingmember 66, such as a wire that passes through one or more eyelets orloops defined by the restraining element. Pulling the retaining member66 proximally disengages the retaining member, thereby releasing therestraining element, which thereby releases upstream frame 22, whichautomatically expands (e.g., radially outward).

Restraining element 64 may alternatively or additionally comprise anyrestraining element configured to reversibly restrain upstream frame 22in its compressed state. For example, (1) element 64 may comprise awrapper (e.g., comprising a fabric) that circumscribes upstream frame22, and retaining member 66 comprises a ripcord that opens the wrapperwhen pulled, or (2) element 64 may comprise a capsule that is slid offof frame 22.

For some applications, when upstream frame 22 expands, it applies aradially-outward force against the atrial walls, but does not apply aradially-outward force against the annulus (e.g., due to the position ofthe upstream frame with respect to the native valve). For someapplications, when upstream frame 22 expands it does not apply aradially-outward force against the atrial walls (e.g., width d1 may beless than a width of the atrium).

Before release and expansion of upstream frame 22, the upstream frame isdisposed around and held immobile with respect to a central rod 68,which provides a separating force that maintains a given distancebetween frames 22 and 24. Typically, downstream frame 24 is alsodisposed around and held immobile with respect to rod 68 while in itscompressed state within sheath 62. Rod 68 therefore serves as a deliverytool, and/or a component thereof. For some applications, implant 20 isdelivered to the heart with frames 22 and 24 separated by that givendistance. For some applications, implant 20 is delivered to the heartwith frames 22 and 24 closer than that given distance, and prior torelease of frame 22 (e.g., subsequently to placement of snares 46against the tissue of the native valve), the distance is increased bymoving frame 22 away from frame 24. For some applications, rod 68 isslidable with respect to (e.g., through) mount 72 (described hereinabovewith reference to FIG. 4D). For some such applications, the distance isincreased by sliding rod 68 distally through mount 72.

When frame 22 is released, the elastic coupling of frame 22 to frame 24reduces the distance between the frames generally at the same time thatframe 22 expands. The arrows in FIG. 4G show frame 22 expanding andmoving closer to frame 24 (i.e., downstream, closer to the nativevalve). As described hereinabove, this behavior sandwiches tissue of thenative valve (e.g., leaflets 12) between upstream frame 22 anddownstream frame 24 (e.g., snares 46 thereof), thereby securing implant20 at the native valve.

Due to the coupling of frame 22 to the upstream portion of sheet 26,expansion of frame 22 pulls the upstream portion of sheet 26 radiallyoutward, typically tensioning the sheet. For some applications, thissandwiches a portion of one or more leaflets 12 between sheet 26 andframe 24 and/or snares 46. For some applications, sheet 26 comprises oneor more elastically-deformable wire braces (not shown; e.g., disposedcircumferentially around conduit 48) that facilitate theradially-outward movement of the sheet.

For some applications, and as shown, a plurality of control wires 70 arecoupled to upstream frame 22 and pass through rod 68 to outside of thebody of the subject. For some applications, the operating physician may,by controlling tension on control wires 70, control expansion of frame22.

Alternatively or additionally, the operating physician may adjustpositioning of frame 22 subsequently to its expansion, e.g., as shown inFIG. 4H. That is, a control force may be applied to upstream frame 22via control wires 70. The control force may pull upstream frame 22radially inward, and/or in an upstream direction.

As described hereinabove, positioning of frame 22 with respect to frame24, while maintaining fluid communication therethrough, is facilitatedby sheet 26. For example, and as shown in FIG. 4H, one side of frame 22may be pulled upstream and/or radially inward by tensioning one or moreof wires 70. For applications in which control wires 70 are used, thecontrol wires are subsequently decoupled from frame 22 and withdrawn viarod 68 (FIG. 4I). For example, each control wire 70 may extend from rod68, loop around a respective portion of frame 22, and pass back into therod, and the decoupling may comprise releasing one end of the wire andpulling on the other end, such that the wire unloops from the frame.

FIG. 4J shows the final position of implant 20 following itsimplantation at the native valve, after rod 68 has been withdrawnproximally through frames 22 and 24 (e.g., via opening 28, conduit 48and lumen 30), and has been withdrawn, along with sheath 62 and trocar60, from the body of the subject. For some applications, restrainingelement 64 is withdrawn via opening 28, conduit 48 and lumen 30, andretaining member 66 is withdrawn alongside implant 20 (i.e., along theoutside of the implant).

As described hereinabove, securing of implant 20 at mitral valve 10 isfacilitated by the elastic coupling of frame 22 to frame 24 whichsandwiches valve tissue between the two frames. It is to be noted thatthis “sandwiching” is typically possible even when diameter d11 issmaller than width d2 (see FIG. 2). It is to be further noted that,although diameter d11 is shown as being smaller than width d2, it mayalternatively be generally equal to, or greater than, width d2.Typically, however, diameter d1 is smaller than width d1. For someapplications, and as shown, securing of implant 20 may alternatively oradditionally be facilitated by a portion of leaflets 12 becomingsandwiched between upstream portion 42 (e.g., snares 46) and sheet 26,which is pulled radially outward when upstream frame 22 expands.

Reference is again made to FIGS. 4A-J. For some applications, upstreamportion 42 of downstream frame 24 is expanded within ventricle 8 (i.e.,downstream of the native valve) and moved upstream against the tissue ofthe native valve without portion 42 having been previously placed at thelevel of coaptation of leaflets 12 (e.g., the steps described withreference to FIGS. 4B-D are omitted). Thus, at least a portion ofdownstream frame 24 is expanded prior to positioning the implant suchthat downstream frame 24 is disposed downstream of the native valve andupstream frame 22 is disposed upstream of the native valve.

It is to be noted that for some applications snares 46 are disposed at alongitudinal portion of downstream frame 24 other than upstream portion42. For example, snares 46 may be disposed at downstream portion 44(e.g., as described for implant 140 with reference to FIGS. 8, 13A-C,14A-C, 15A-17, and/or 20A-C, mutatis mutandis), or between upstreamportion 42 and downstream portion 44. For some such applications themethod of implantation is adjusted to suit the position of snares 46.

Reference is made to FIGS. 5-8, which are schematic illustrations ofrespective implants, each comprising an upstream frame elasticallycoupled to a downstream frame and a flexible sheet that provides fluidcommunication between the two frames, in accordance with someapplications of the invention. Each of the implants (and its components)is typically identical to implant 20 (and its identically-namedcomponents), except where noted, and is implanted as described forimplant 20, mutatis mutandis. For each figure, the state of the implanton the left side of the figure may be considered an extended state, andthe state of the implant on the right side of the figure may beconsidered a contracted state.

FIG. 5 shows an implant 80 comprising upstream frame 22, downstreamframe 24, and a flexible sheet 86, and is typically identical to implant20 except that the elastic coupling of frame 22 to frame 24 is providedby one or more elastic tethers 82. Tethers 82 are typically flexible.Each tether is coupled at one end to frame 22 and at the other end toframe 24. Typically, but not necessarily, each tether 82 is coupled toupstream portion 42 of frame 24 and/or to downstream end 34 of frame 22.When tethers 82 reduce the distance between frames 22 and 24 fromdistance d6 to distance d7, sheet 86, which is typically not elasticitself and therefore has a fixed length (unlike sheet 26 of implant 20),rumples. For some applications, and as shown, sheet 86 is configured torumple in a pre-determined and/or controlled fashion (e.g., to fold), soas not to interfere with fluid communication through conduit 48 definedby the sheet. For example, at least a portion of the sheet may bepre-creased and/or heat-set such that it folds neatly when the distancebetween the frames 22 and 24 is reduced. The sheet thereby defines afolding zone 84 in which, for some applications, a first fold of thesheet may touch a second fold of the sheet when the implant is in itscontracted state.

FIG. 6 shows an implant 100 comprising an upstream frame 102, downstreamframe 24, and flexible sheet 86, and is typically identical to implant80 except that the elastic coupling of the upstream frame to thedownstream frame is provided by the upstream frame. Upstream frame 102is configured to provide a plurality of springs 108 (e.g., cantileversprings), which are coupled to downstream frame 24 via a respectiveplurality of tethers 106. Tethers 106 are typically inelastic, but forsome applications may be elastic. Tethers 106 are typically flexible.Typically, springs 108 are defined at upstream end 32 of upstream frame102 (the reference numeral 32 is used for clarity of reference betweenframe 102 and frame 22 described hereinabove). For example, and asshown, upstream frame 102 may define a plurality of regularly-tiledcells (e.g., two-dimensional shapes) (e.g., like the other upstreamframes described herein), and each spring 108 may be defined by arespective one of the cells, e.g., utilizing the shape-memory propertyof the material from which the frame is formed. In the extended state ofimplant 100 (left side of FIG. 6) springs 108 are in anelastically-deformed state, and in the contracted state (right side ofFIG. 6) springs 108 are in a less deformed state (e.g., may be in arelaxed state). For some applications, tethers 106 pass throughrespective holes in sheet 26 as they pass from frame 22 to frame 24.Alternatively, springs 108 may be defined at downstream end 34 ofupstream frame 102, or elsewhere on the upstream frame.

FIG. 7 shows an implant 120 comprising an upstream frame 122, downstreamframe 24, and a flexible sheet 126, and is typically identical toimplant 100 except that the elastic coupling of the upstream frame tothe downstream frame is provided by the upstream frame in a differentmanner to which the upstream frame of implant 100 provides elasticcoupling. Upstream frame 122 is configured to provide a plurality ofsprings 128 (e.g., cantilever springs), which are not coupled todownstream frame by tethers. Instead, the shape of sheet 126 and itscoupling to frames 122 and 24 positions springs 128, which are typicallydefined at downstream end 34 of frame 122, such that the springs providethe elastic coupling by pulling the sheet in an upstream direction. Inthe contracted state (right side of FIG. 7) portions of sheet 126 thathave been pulled in the upstream direction are visible. In thecontracted state, sheet 126 is thereby under tension, and thereforetypically does not require folding zone 84.

FIG. 8 shows an implant 140 comprising upstream frame 22, a downstreamframe 144, and a flexible sheet 146. Frame 144 defines tubular body 40described hereinabove, which has an upstream portion 42 and a downstreamportion 44. A plurality of snares 148 protrude radially outward fromdownstream portion 44, thereby defining diameter d11 describedhereinabove, mutalis mutandis.

Snares 148 may alternatively or additionally protrude outward fromanother longitudinal portion of frame 144, such as upstream portion 42or a longitudinal portion between portions 42 and 44.

Typically, snares 148 protrude outward in an upstream direction (i.e.,toward upstream frame 22), which is hypothesized to facilitate captureof native valve leaflets, as described hereinabove, mutatis mutandis.Sheet 146 is coupled to upstream end 32 of upstream frame 22, anddefines a conduit 147 that provides fluid communication between anopening 150 defined by frame 22 and lumen 30 defined by body 40. It isto be noted that both upstream end 32 and downstream end 34 of frame 22may be considered to define a respective opening. Opening 150 is definedby upstream end 32, and a second opening 150′ is defined by downstreamend 34.

In the contracted state of implant 140, at least upstream portion 42(e.g., an upstream end) of downstream frame 144 is disposed upstream ofsecond opening 150′ (e.g., within a space 154 defined by upstream frame22). Typically, in the extended state, less (e.g., none) of frame 144 isdisposed upstream of opening 150′ (e.g., within space 154). Duringimplantation of implant 140, tissue of the native valve becomessandwiched between snares 148 and upstream frame 22, e.g., using one ormore of the mechanisms described herein.

It is hypothesized that the coupling of sheet 146 to upstream end 32 offrame 22 provides improved blood flow compared to a similar device inwhich the sheet is coupled to downstream end 34 of frame 22, because inthe latter a zone 152 may be defined in the vicinity of downstream end34 in which blood flow is reduced, increasing the likelihood ofthrombosis formation. For example, zone 152 may be within space 154,downstream of upstream portion 42 of frame 144, and upstream ofdownstream end 34 of frame 22. It is to be noted that the scope of theinvention includes coupling of sheet 146 to other regions of frame 22,such as slightly downstream of upstream end 32 (e.g., a quarter, athird, halfway, two-thirds, or three-quarters of the way towarddownstream end 34).

Reference is now made to FIGS. 9-10, which are schematic illustrationsof implants 160 and 180, which are typically identical to implant 20,except for the inclusion of atraumatic modifications, in accordance withsome applications of the invention. Implant 160 comprises a downstreamframe 164 that is typically identical to downstream frame 24, describedhereinabove, except that downstream portion 44 is curved inward so as toreduce a likelihood of the downstream portion damaging tissue of thenative valve, such as chordae tendineae. Implant 180 comprises adownstream frame 184 that is typically identical to downstream frame 24,except that snares 186 of implant 180 are curved back on themselves soas to reduce a likelihood of damaging tissue of the native valve, suchas leaflets or chordae tendineae. For some applications, and as shown,distal ends of snares 186 point downstream. It is to be noted that theatraumatic modifications shown in FIGS. 9-10 may be made (individuallyor together) to any of the implants described herein.

Reference is now made to FIG. 11, which is a schematic illustration ofan implant 200, in accordance with some applications of the invention.Implant 200 is typically identical to implant 20, except where noted. Adownstream frame 204 comprises generally tubular body 40, describedhereinabove. Snares 206 extend radially outward from body 40, typicallyfrom upstream portion 42 (but alternatively may extend from otherpositions of body 40, such as downstream portion 44).

Snares 206 are loops that extend radially away from body 40,circumferentially around body 40, and radially back toward body 40,thereby defining lobes that extend around circumferential portions ofbody 40. Each snare 206 typically extends from a first cell of the frameof body 40, circumferentially past at least one (e.g., at least two,such as at least three) other cells, and radially back to another cell.

Each snare typically extends more than 20 degrees around body 40 (e.g.,more than 40 degrees, such as more than 60 degrees). Purely forillustrative purposes, FIG. 11 shows each snare 206 extending abouthalfway around body 40. Snares 206 facilitate sandwiching of the tissueof the native valve as described hereinabove, mutatis mutandis.

For some applications, snares 206 are used in combination with snares46, described hereinabove. For example, an implant may comprise onesnare 206 and a plurality of snares 46.

Typically, when the implant comprises one or more snares 206 (as opposedto solely snares 46), the implant is placed in a particular rotationalorientation with respect to the native valve, e.g., before deployment.For example, snares 206 may be aligned with the a2 and/or p2 scallops ofleaflets 12 e.g., so as to reduce interaction with chordae tendineae.Typically, for the example in which the implant comprises one snare 206and a plurality of snares 46, the snare 206 is aligned with the a2scallop of the anterior leaflet.

Reference is made to FIGS. 12A-C, which are schematic illustrations ofdelivery and implantation of implant 20, in accordance with someapplications of the invention. As described hereinabove, FIGS. 4A-J showtransapical delivery and implantation of implant 20, but the scope ofthe invention includes other delivery routes. To illustrate this, FIGS.12A-C show transfemoral transseptal delivery and implantation of implant20. It is to be understood that the same techniques may be used forother transseptal and transatrial routes, mutatis mutandis.

A catheter 220 (e.g., a sheath) is advanced transfemorally and via theinferior vena cava into right atrium 7 of the heart, and then into leftatrium 6 via transseptal puncture, as is known in the art.

Compared to the techniques described with reference to FIGS. 4A-J, inits delivery state the orientation of implant 20 is reversed withrespect to the catheter through which it is delivered. Whereas fortransapical delivery frame 22 is disposed closer to the distal end ofthe catheter than is frame 24, in FIGS. 12A-C, frame 24 is closer to thedistal end.

The step shown in FIG. 12A corresponds generally to the step shown inFIG. 4B, mutalis mutandis. That is, implant 20 has been delivered tobetween leaflets 12, and upstream portion 42 and/or snares 46 ofdownstream frame 24 have been exposed and have begun to expand, whileupstream frame 22 is maintained in its compressed delivery state. Incontrast to FIG. 4B, in FIG. 12A, (1) downstream frame 24 is initiallymaintained in its compressed delivery state by being disposed in acapsule 222, and upstream portion 42 and/or snares 46 are exposed bymoving the capsule distally downstream; and (2) upstream frame 22 ismaintained in its compressed delivery state by being disposed withincatheter 220.

FIG. 12B corresponds generally to the step shown in FIG. 4F, mutatismutandis. That is, FIG. 12 shows frame 24 having automatically fullyexpanded into its expanded state responsively to downstream portion 44of frame 24 having been fully exposed from capsule 222, subsequently to(1) movement of the implant downstream until leaflets 12 coapt aboveupstream portion 42 and/or snares 46 (e.g., against sheet 26, frame 24,and/or catheter 220), (2) optional further expansion of upstream portion42 and/or snares 46 by moving capsule 222 further downstream, and (3)movement of implant upstream such that portion 42 and/or snares 46contact and apply an upstream force to tissue of the native valve.

FIG. 12C corresponds generally to the step shown in FIG. 4I, mutatismutandis. That is, subsequently to release and expansion of upstreamframe 22 (by deployment out of catheter 220), optionally controlled by aplurality of control wires 224 coupled to frame 22 and passing throughthe catheter to outside the body of the subject, the control wires aredecoupled from frame 22 and withdrawn via the catheter. FIG. 12C alsothereby shows the final position of implant 20 at the native valve.

Reference is again made to FIGS. 1A-12C. As described hereinabove, foreach implant, the downstream frame is distinct from the upstream frame.For some applications, there is no metallic connection between theupstream and downstream frames. For some applications, there is nometallic connection between the upstream and downstream frames exceptfor flexible tethers, which may be metallic.

For some applications, the upstream frame (e.g., the upstream frame ofimplant 140, or another upstream frame described herein) may be coveredor lined (e.g., partially or entirely) with a covering, such as afabric. For some applications, the covering may comprise the samematerial as the flexible sheet. For some such applications, a continuouspiece of material may define the covering and the flexible sheet.

For some applications, in addition to or in place of elastic coupling offrame 22 to frame 24, sandwiching may be achieved by the operatingphysician actively reducing the distance between the frames, such as bytensioning one or more tethers. For some such applications, this may beachieved using apparatus and/or methods described in InternationalPatent Application PCT/IL2014/050087, filed Jan. 23, 2014, which isincorporated herein by reference.

Reference is made to FIGS. 13A-C, and 14A-C, which are schematicillustrations of implants that each comprise an upstream frame (e.g., anupstream support), a downstream frame (e.g., a prosthetic valve frame),and a flexible sheet connecting the upstream and downstream frames, inaccordance with some applications of the invention.

FIGS. 13A-C are schematic illustrations of an implant 240, comprisingupstream frame 22, a downstream frame 244, and a flexible sheet 246.Downstream frame 244 comprises a plurality of snares 248 at a downstreamend of the frame. For some applications, downstream frame 244 isidentical to downstream frame 144 described hereinabove, and/or snares248 are identical to snares 148 described hereinabove.

FIG. 13A shows implant 240 in a compressed state thereof, in which bothframe 22 and frame 244 are in respective compressed states thereof(e.g., for percutaneous delivery of the implant).

Typically, frame 22 and/or frame 244 are generally cylindrical when inthe compressed state. In the compressed state of implant 240, sheet 246typically extends longitudinally between frames 22 and 244, andarticulatably couples the frames to each other, thereby defining anarticulation zone 247 between the frames. For some applications thisarticulation is hypothesized to facilitate percutaneous (e.g.,transluminal) delivery of the implant, by allowing the compressedimplant to articulate as it passes bends in the percutaneous path to theheart.

FIGS. 13B-C show implant 240 in an expanded state thereof, in which bothframe 22 and frame 244 are in respective expanded states thereof (e.g.,an implanted state of the implant). FIG. 13B is a perspective view, andFIG. 13C is a cross-sectional view. Frame 244 defines a lumen 250therethrough, in which prosthetic leaflets 50 (described hereinabove)are disposed and coupled to frame 244, e.g., as described for otherimplants herein. For clarity, leaflets 50 are not shown in FIG. 13A-C or14A-B.

In the expanded state of implant 240, upstream portion (e.g., anupstream end) 42 of downstream frame 244 is disposed longitudinallyupstream of opening 150′ of upstream frame 22.

That is, implant 240 has a central longitudinal axis, and upstreamportion 42 is disposed further upstream along the longitudinal axis thanis opening 150′. This typically occurs because expansion of upstreamframe 22 toward its expanded state pulls valve frame 244 longitudinallyin an upstream direction, by pulling sheet 246 radially outward.Typically, in the expanded state of implant 240, a diameter d15 of frame244 is smaller than diameter d2 of frame 22, and sheet 246 is annular,extending radially inward from frame 22 to frame 244, and iscircumferentially attached to frame 244 at a longitudinal site 254 offrame 244. Typically, sheet 246 provides fluid sealing between frames 22and 244.

Implant 240 is percutaneously advanced, in its compressed state, to thenative valve, and is deployed such that snares 248 are disposeddownstream of the native valve (i.e., in the ventricle) and upstreamframe 22 is disposed upstream of the native valve (i.e., in the atrium),e.g., sandwiching tissue of the native valve between the snares and theupstream frame (and/or between the snares and sheet 246). FIG. 14Cillustrates such implantation of a similar implant, mutatis mutandis.

FIGS. 14A-C are schematic illustrations of an implant 260, comprising anupstream frame 262, a downstream frame 264, and two flexible sheets 266a and 266 b, which couple the upstream frame to the downstream frame.Downstream frame 264 comprises a plurality of snares 268 at a downstreamend of the frame. For some applications, downstream frame 264 isidentical to downstream frame 244 and/or downstream frame 144 describedhereinabove, and/or snares 266 are identical to snares 248 and/or 148described hereinabove.

Upstream frame 262 is similar to upstream frame 22 describedhereinabove, except that frame 262 is not necessarily widest at amid-portion thereof (compare to FIG. 1A and description thereof).

It is to be noted that for some applications, frame 22 of implant 240and frame 262 of implant 260 may be substituted for each other.

FIGS. 14A-C show implant 260 in an expanded state thereof, in which bothframe 262 and frame 264 are in respective expanded states thereof (e.g.,an implanted state of the implant). FIG. 14A is a perspective view, FIG.14B is a cross-sectional view, and FIG. 14C shows implant 260 havingbeen implanted at native valve 10. Typically, implant 260 is similar toimplant 240, except that instead of a single sheet 246, implant 260comprises a first flexible sheet 266 a, which may be identical to sheet246, and further comprises a second flexible sheet 266 b.

In the expanded state of implant 260, upstream portion (e.g., anupstream end) 42 of downstream frame 264 is disposed longitudinallyupstream of opening 150′ of upstream frame 262.

That is, implant 260 has a central longitudinal axis, and upstreamportion 42 is disposed further upstream along the longitudinal axis thanis opening 150′. This typically occurs because expansion of upstreamframe 262 toward its expanded state pulls valve frame 264 longitudinallyin an upstream direction, by pulling sheet 266 a and/or sheet 266 bradially outward. Typically, in the expanded state of implant 260, adiameter of frame 264 is smaller than a diameter d2 of frame 262, e.g.,as described for implant 240, mutatis mutandis. That is, the diameter offrame 264 is smaller than the opening defined by the downstream end offrame 262. Sheet 266 a extends radially inward from frame 262 to frame264, and is circumferentially attached to frame 264 at a firstlongitudinal site 274 a of frame 264. For some applications, sheet 266 ais identical to sheet 246 described hereinabove, mutatis mutandis.

Sheet 266 b also extends radially inward from frame 262 (e.g., from thesame or a different point of frame 262), and is circumferentiallyattached to frame 264 at a second longitudinal site 274 b of frame 264.Typically, longitudinal site 274 b is closer to upstream portion 42 thanis longitudinal site 274 b. For example, longitudinal site 274 b may beat least 2 mm and/or less than 8 mm closer to upstream portion 42 thanis longitudinal site 274 b (e.g., 2-12 mm closer, or at least 3 mmcloser, such as 3-10 mm closer). Further typically, longitudinal site274 b is at upstream portion 42.

A chamber 276 (e.g., a closed chamber) that circumscribes frame 264 isdefined between sheets 266 a and 266 b (shown in cross-section in FIGS.14B-C, and also shown by cutaway in FIG. 14A). Chamber 276 is typicallytoroidal. Subsequently to implantation of implant 260, and as shown inFIG. 14C, tissue formation typically occurs within chamber 276, e.g.,due to blood entering the chamber 276 by passing through the flexiblesheets (e.g., at least one of the sheets is at least partiallyblood-permeable). For some applications this tissue formation ishypothesized to gradually increase rigidity of implant 260. It is to benoted that for implant 240 (FIGS. 13A-C), a recessed region 256circumscribes upstream portion 42 of downstream frame 264. Recessedregion 256 is downstream of (i.e., below) upstream portion 42 andupstream of (i.e., above) opening 150′. This recessed region is reduced(e.g., eliminated) in implant 260. The reduction of region 256 isimplant 260 is hypothesized to improve blood flow dynamics through theimplant, thereby reducing a likelihood of thrombus formation.

Reference is made to FIGS. 15A-C, 16A-D, and 17, which are schematicillustrations of an implant 280, and implantation thereof, in accordancewith some applications of the invention. FIG. 15A shows a perspectiveview of implant 280, FIG. 15B shows a cutaway view of the implant, andFIG. 15C shows an exploded view of frame components of the implant.FIGS. 16A-D and 17 show steps in the implantation of implant 280 atmitral valve 10.

Implant 280 comprises an upstream support 282, a valve frame 284, asnare frame 288, and at least one flexible sheet 286. Sheet 286 couplessnare frame 288 to valve frame 284, and as shown, typically furthercouples upstream support 282 to the valve frame. For some applications,the coupling of upstream support 282 to valve frame 284 via sheet 286 issimilar to that of the coupling provided by sheet 266 b of implant 260,mutatis mutandis. Sheet 286 typically provides fluid sealing betweensupport 282 (e.g., the frame thereof) and frame 284, and furthertypically provides fluid sealing between frames 284 and 288. For someapplications, a single sheet 286 extends from snare frame 288, alongvalve frame 284, and to upstream support 282, thereby coupling the threeframes together in the configuration shown. The coupling of the framesvia sheet 286 advantageously provides some limited movement (e.g.,articulation) between the frames, at least in some states of theimplant. For example, as described hereinbelow, this couplingfacilitates expansion of snare frame 288 while valve frame 284 remainsat least in part compressed.

Snare frame 288 typically comprises an annular portion 290 and aplurality of snares 292 that extend from the annular portion. FIG. 15Cshows snare frame 288 in an expanded state thereof. In the expandedstate of snare frame 288, snares 292 protrude radially outward and in anupstream direction. Typically, annular portion 290 is defined by arepeating pattern of struts, such as in a zig-zag pattern (as shown).Typically, at least annular portion 290 provides shape memory to snareframe 288, which is delivered to the heart constrained in a compressedstate, and which automatically moves toward its expanded state whenunconstrained (e.g., as described hereinbelow).

Valve frame 284 is a tubular frame that defines a lumen therethrough,e.g., as described herein for other valve frames. For some applications,valve frame 284 is identical to other valve frames described herein.

Upstream support 282 is annular, and defines two annular portions: anupper annular portion 294 and a lower annular portion 296 that iscircumferentially coupled to the upper annular portion (e.g., at aperimeter of upstream support 282). Upper annular portion 294 may beconsidered to be a first layer of support 282, and downstream annularportion 296 may be considered to be a second layer of the support. Forsome applications, upstream support 282 is cut from a single piece ofmetal (typically Nitinol), and in a compressed state of the upstreamsupport, struts that form lower annular portion 296 intercalate withstruts that form upper annular portion 294. For some applications, andas shown, the struts that define upper annular portion 294 are arrangedas chevrons that repeat in a circumferential pattern (e.g., a zigzagpattern). For some applications, and as shown, the struts that definelower annular portion 296 are arranged as chevrons that repeat in acircumferential pattern.

For some applications, and as shown, each chevron of upper annularportion 294 is coupled to a chevron of lower annular portion 296 at theperimeter of support 282, and is slightly differently sized to thatchevron of the lower annular portion.

As shown in FIG. 15B, upstream support 282 is coupled to valve frame 284such that (i) upper annular portion 294 extends radially outward from afirst longitudinal site 298 of the prosthetic valve frame toward aperimeter 300 of the upstream support, and (ii) lower annular portion296 extends radially inward from the upper annular portion toward asecond longitudinal site 299 of the prosthetic valve frame. Secondlongitudinal site 299 is downstream of first longitudinal site 298.Typically, and as shown, first longitudinal site 298 is at an upstreamend of valve frame 284. Typically, and as shown, lower annular portion296 does not contact valve frame 284, and an inner perimeter 293 ofportion 296 defines a free edge.

For some applications, upstream support 282 is coupled to valve frame284 such that upper annular portion 294 extends, from first longitudinalsite 298, radially outward in a downstream direction (e.g., as shown).For some applications, upstream support 282 is coupled to valve frame284 such that lower annular portion 296 extends, from the upper annularportion, radially inward in a downstream direction (e.g., as shown).

Lower annular portion 296 is deflectable with respect to upper annularportion 294, and is typically more movable with respect to valve frame284 than is upper annular portion 296. For example, lower annularportion 296 may be articulatably coupled to upper annular portion 294,and/or may be more flexible than the upper annular portion (e.g., strutsthat form the lower annular portion may be thinner than those that formthe upper annular portion, as shown). As described in more detailhereinbelow, it is hypothesized that this configuration facilitatessealing of support 282 against the upstream surface of mitral valve 10(e.g., the mitral annulus) by maintaining contact between lower annularportion 296 and the upstream surface of the mitral valve, irrespectiveof an angle that upper annular portion 294 is disposed with respect tovalve frame 284.

For some applications, the struts of upper annular portion 294 have atransverse cross-sectional area 295 of 0.25-1 mm{circumflex over ( )}2.For some applications, the struts of lower annular portion 296 have atransverse cross-sectional area 297 of 0.04-0.2 mm{circumflex over( )}2. For some applications, support 282 has a diameter (defined by itsperimeter) of 50-70 mm.

For some applications, sheet 286 extends over an upper surface of upperannular portion 294, around perimeter 300, and over a lower surface oflower annular portion 296 (thereby serving as a covering of portions 294& 296). While implant 280 is implanted at mitral valve 10, theabove-described configuration of upstream support 282 thereby holds thecovering against the upstream surface of the mitral valve, therebyfacilitating sealing.

The bubble of FIG. 15B shows an optional arrangement for the coupling ofsupport 282 to frame 284, in accordance with some applications of theinvention. A first sheet portion 286 a covers at least part of an innersurface of valve frame 284 (e.g., serves as an inner covering, or aliner, of at least part of the valve frame). A second sheet portion 286b covers at least part of an outer surface of valve frame 284 (e.g.,serves as an outer covering of at least part of the valve frame). Athird sheet portion 286 c covers at least part of upstream support 282(e.g., at least part of upper annular portion 294 thereof). Eitherportion 286 a or portion 286 b extends past an upper end of valve frame284, and covers at least part of upstream support 282, e.g., at leastpart of upper annular portion 294 thereof (FIG. 15B shows portion 286 bdoing this). The other one of portion 286 a and portion 286 b does notextend to the upper end of valve frame 284 (FIG. 15B shows portion 286 adoing this). Portion 286 c extends past an inner edge of support 282(e.g., an inner edge of upper annular portion 294), and covers at leastpart of upstream support 282.

At a connection point 310, portion 286 c (i) is connected (e.g.,sutured) to portion 286 a or 286 b (whichever does not extend to theupper end of valve frame 284), and (ii) is typically also connected tothe valve frame. (Typically, portion 286 a is also connected to valveframe 284 at point 310.) At a connection point 312, portion 286 a or 286b (whichever extends to support 282) (i) is connected (e.g., sutured) toportion 286 c, and (ii) is typically also connected to support 282.(Typically, portion 286 c is also connected to support 282 at point312.) It is to be noted that such an arrangement results in valve frame284 being coupled to support 282 via two flexible sheets 286 (each ofthe sheets being defined by one of the sheet portions).

It is hypothesized that such an arrangement of sheet portions, and suchattachment of the sheet portions to the frames and to each other,provides strong and durable coupling of valve frame 284 to support 282via a flexible sheet.

A technique for implanting implant 280 is now described with referenceto FIGS. 16A-D.

Implant 280 is percutaneously (e.g., transluminally, such astransfemorally) delivered to mitral valve 10 while the implant is in acompressed state (e.g., within a delivery tube 302, such as a catheter),such that at least snare frame 288 is downstream of the mitral valve(i.e., within ventricle 8). For some applications, in the compressedstate, snare frame 288 is inverted inside-out, such that snares 292 aredownstream of (e.g., distal to) annular portion 290, and the snare frameis downstream of (e.g., distal to) valve frame 284. FIG. 16A showsimplant 280 having been delivered in this manner, and having beenpartially deployed from delivery tube 302 such that part of snare frame288 (e.g., part of snares 292) is exposed.

Once snare frame 288 is fully exposed from delivery tube 302, the snareframe automatically expands toward its expanded state, e.g., byre-inverting, such that snares 292 are upstream of annular portion 290(FIG. 16B). The coupling of snare frame 288 to valve frame 284 via sheet286 facilitates expansion of the snare frame while the valve frameremains at least partly compressed within delivery tube 302. Forexample, while valve frame 284 remains at least partly compressed withindelivery tube 302, an angle alpha_3 between snare frame 288 (e.g.,snares 292 thereof) and a central longitudinal axis of implant 280 istypically greater than of the would be in an otherwise similar implantin which the snare frame is rigidly coupled to the valve frame.Similarly, while an upstream portion of valve frame 284 remainscompressed within delivery tube 302, an angle alpha_4 between snareframe 288 (e.g., snares 292 thereof) and a downstream portion of thevalve frame is typically greater than it would be in an otherwisesimilar implant in which the snare frame is rigidly coupled to the valveframe. It can be understood from this that snare frame 288 is typicallycoupled to valve frame 284 such that angle alpha_3 is independent ofangle alpha_4.

These increased angles facilitate engagement of tissue of mitral valve10 (e.g., leaflets 12) when implant 280 is subsequently moved upstream(FIG. 16C). For example, the increased angles result in snares 292reaching out further laterally, and/or result in a greater space betweenthe snares and valve frame 284 in which leaflets 12 may become disposed.

Following the upstream movement of implant 280, upstream support 282, inits compressed state within delivery tube 302, is upstream of mitralvalve 10 (i.e., in atrium 6). For some applications, the coupling ofupstream support 282 to valve frame 284 via sheet 286 facilitatesexpansion of the valve frame while the upstream support 282 remainscompressed. FIG. 16D shows implant 280 fully deployed at mitral valve10, after upstream support 282 has been deployed from delivery tube 302.

Lower annular portion 296 of upstream support 282 is disposed against anupstream surface of the mitral valve and, as described hereinabove,facilitates sealing (i.e., inhibits paravalvular leakage).

It is to be noted that therefore, for some applications, when implantingimplant 280 (or another implant in which snares are coupled to the valveframe in the manner described for implant 280), the following steps areperformed: (i) The implant is percutaneously delivered via delivery tube302. (ii) While at least a portion (e.g., an upstream portion) of thevalve frame remains disposed within the delivery tube, the snares aredeployed from the distal end of the delivery tube such that the snaresprotrude radially outward and form angle alpha_3 with the axis, andangle alpha_4 with the valve frame. (iii) Subsequently, tissue of thenative valve is engaged using the snares (e.g., by moving the implant inan upstream direction). (iv) Subsequently, by deploying more of thevalve frame (e.g., the remainder of the valve frame) from the catheter,angle alpha_4 is reduced by at least 30 percent (e.g., by at least 50percent), while angle alpha_3 is not changed by more than 10 percent(e.g., angle alpha_3 is changed by less than 8 percent, e.g., by lessthan 5 percent), such as while angle alpha_3 remains constant.

For some applications, in the absence of lower annular portion 296,upstream support 282 would contact the upstream valve surface only atperimeter 300. Lower annular portion 296 increases the contact surfacearea between upstream support 282 and the upstream valve surface.

Upper annular portion 294 is resilient (e.g., has shape memory) and isthus biased to assume a particular shape. For example, and as shown,upper annular portion 294 may be frustoconical, with its wider baselower than (e.g., downstream of) its narrower base. This characteristicfacilitates upstream annular portion 294 serving as a spring that istensioned by sandwiching of tissue between the upstream annular portionand snare frame 288 during implantation, and thereby facilitates secureanchoring of the implant at the mitral valve. Upstream annular portionfacilitates this anchoring via tension on sheet 286.

Tensioning of upper annular portion 294 typically results in deflectionof upper annular portion 294 with respect to valve frame 284 (e.g.,perimeter 300 becomes more upstream with respect to site 298). This mayalso occur during the cardiac cycle. The deflectability of lower annularportion 296 with respect to upper annular portion 294 facilitates thelower annular portion remaining in contact with the upstream valvesurface despite the deflection of the upper annular portion with respectto the upstream valve surface. Thus, for some applications, an anglealpha_5 between upper annular portion 294 and lower annular portion 296when the implant is in a rest state (e.g., an unconstrained shape, suchas when the implant is on a table-top) (FIG. 15B) is greater than anangle alpha_6 between the annular portions when the implant is implantedand tissue of the native valve is disposed between upstream support 282and snare frame 288. For some applications, angle alpha_5 is 45-90degrees.

It is to be noted that for some applications snares 292 (e.g., snareframe 288) may be coupled via a flexible sheet to other prostheticvalves (e.g., to other valve frames described herein), including thosecomprising a valve frame that is rigidly coupled to an upstream support,and those comprising a valve frame that is not coupled to an upstreamsupport (e.g., prosthetic valves that are configured to beintracorporeally coupled to an upstream support, and prosthetic valvesthat are configured to be implanted without an upstream support).

It is to be noted that for some applications upstream support 282 may beused in combination with other prosthetic valves (e.g., with other valveframes described herein), including those comprising a valve frame thatis rigidly coupled to snares or tissue-engaging elements. It is to benoted that for some applications upstream support 282 may be rigidlycoupled to valve frame 284 (or to another valve frame).

Reference is now made to FIG. 17, which shows implant 280, in itscompressed state, being delivered to the heart via delivery tube 302(e.g., a catheter), in accordance with some applications of theinvention. In the compressed state of implant 280, valve frame 284 istypically disposed collinearly between upstream support 282 and snareframe 288. The connection of snare frame 288 to valve frame 284 viasheet 286 typically provides articulation between the snare frame andthe valve frame while implant 280 is in its compressed state. That is,in the compressed state of implant 280, sheet 286 typically extendslongitudinally between frames 288 and 284, thereby defining anarticulation zone 289 a between these frames. While implant 280 is inits compressed state, sheet 286 further typically defines anarticulation zone 289 b between valve frame 284 and upstream support282, e.g., as described hereinabove for implant 240, mutatis mutandis.Therefore, for some applications, in its compressed state, implant 280has three rigid segments (defined by support 282, frame 284, and frame288, respectively) in tandem, and two articulation zones separating therigid segments.

For some applications, articulation zone 289 a separates snare frame 288from valve frame 284 by at least 1.5 mm (e.g., 1.5-10 mm, e.g., 1.5-5mm, such as 2-5 mm). For some applications, articulation zone 289 aseparates valve frame 284 from upstream support 282 by at least 1.5 mm(e.g., at least 3 mm, e.g., 3-10 mm, e.g., 3-8 mm, such as 3-5 mm).

For some applications this articulation is hypothesized to facilitatepercutaneous (e.g., transluminal) delivery of implant 280, by allowingthe compressed implant to articulate as it passes bends in thepercutaneous path to the heart. FIG. 17 shows articulation zones 289 aand 289 b facilitating passage of implant 280 through a bend in deliverytube 302, e.g., in the vicinity of fossa ovalis 5 in the interatrialseptum of the heart. For some applications, delivery tube 302 is capableof forming a bend 291 having a radius of curvature of less than 15 mm(e.g., less than 13 mm) and/or more than 5 mm (e.g., 5-15 mm, e.g.,10-15 mm, such as 10-12 mm), and implant 280, in its compressed state,is advanceable through bend 291.

For some applications, in its compressed state, implant 280 has a lengthof at least 25 mm (e.g., 25-50 mm), such as at least 30 mm. For someapplications, in its compressed state, implant 280 has a greatest widththat is at least 50 percent (e.g., 50-90 percent), such as at least 75percent (e.g., 75-98 percent, such as 75-90 percent) of the internaldiameter of delivery tube 302. For some applications, in the compressedstate of implant 280, upstream support 282, valve frame 284, and snareframe 288, each have a respective width d21 that is at least 50 percent(e.g., 50-90 percent), such as at least 75 percent (e.g., 75-98 percent,such as 75-90 percent) of the internal diameter of delivery tube 302. Itis hypothesized that an implant having the same length and width, butnot having articulatable coupled segments, would not be advanceablethrough bend 291.

For some applications, in the compressed state of implant 280, noindividual rigid segment has a length (measured along the longitudinalaxis of the implant) that is greater than 22 mm. For some applications,in the compressed state of implant 280, a sum of (i) a length d20′ ofthe rigid segment defined by support 282, (ii) a length d20″ of therigid segment defined by frame 284, and a length d20′″ of the rigidsegment defined by frame 288, is at least 35 mm.

Typically, a delivery tool 304, reversibly couplable to implant 280, isused to advance the implant to the heart (e.g., via delivery tube 302).Typically, implant 280 is delivered with snare frame 288 disposeddistally to valve frame 284, and upstream support 282 disposedproximally to the valve frame, e.g., such that snare frame 288 emergesfrom tube 302 first.

For some applications, implant 280 is delivered with frame 288 invertedand folded up against the outside of frame 284. For such applications,it is hypothesized that the coupling of these two frames via sheet 286facilitates this folding. For example, for some applications frame 288(e.g., the entire length of frame 288) may be disposed flat againstframe 284, thereby resulting in a small maximum width of the implant inits compressed state. In contrast, a different sort of coupling mightresult in the fold between the frames having a radius of curvature thatincreases the width of the implant, at least in the area of couplingbetween frames 288 and 284.

It is to be noted that for some applications the apparatus andtechniques described with reference to FIGS. 15A-17 may be used incombination with those described in PCT patent application publicationWO 2014/115149 to Hammer et al., which is incorporated herein byreference.

Reference is made to FIGS. 18 and 19A-B, which are schematicillustrations of frames of upstream supports, in accordance with someapplications of the invention. FIG. 18 shows a frame of an upstreamsupport 642, and FIGS. 19A-B show a frame of an upstream support 662.Upstream supports 642 and 662 may be used in place of other upstreamsupports described herein.

Upstream support 642 is typically identical to upstream support 282except where noted otherwise. Upstream support 642 is annular, anddefines two annular portions: an upper annular portion 654 and a lowerannular portion 656 that is circumferentially coupled to the upperannular portion (e.g., at a perimeter of upstream support 642). Asdescribed for support 282, for some applications struts 655 that formupper annular portion 654 of support 642 are arranged as chevrons thatrepeat in a circumferential pattern (e.g., a zigzag pattern). Incontrast to support 282, struts 657 that form lower annular portion 656of support 642 are typically individual rods 658 that protrude radiallyinward from the point at which they are coupled to upper annular portion654 (e.g., from the perimeter of the frame). It is to be noted that theframe of support 642 (e.g., the struts of its upper and lower annularportions) is typically covered with a covering (e.g., described forsupport 282), such that the support generally resembles support 282(e.g., as shown in FIGS. 15A-C), mutatis mutandis.

Support 442 generally functions as described for support 282. It ishypothesized that, for some applications, the different configuration ofthe lower annular portion of support 642 compared to that of support 282facilitates independent movement of different regions of lower annularportion 656, thereby improving its conformation to the anatomy and/orsealing against the anatomy. For some applications, this is furtherfacilitated by each rod 658 being shaped as a spring (as shown), therebyincreasing flexibility of the rod.

Upstream support 662 is typically identical to upstream support 642except where noted otherwise. Upstream support 662 is annular, anddefines two annular portions: an upper annular portion 674 and a lowerannular portion 676 that is circumferentially coupled to the upperannular portion (e.g., at a perimeter of upstream support 662). Asdescribed for support 282 and 642, for some applications struts 675 and679 that form upper annular portion 674 of support 662 are arranged aschevrons that repeat in a circumferential pattern (e.g., a zigzagpattern). For some applications, and as shown, struts 677 that formlower annular portion 676 of support 662 are individual rods 678 thatprotrude radially inward from the point at which they are coupled toupper annular portion 664 (e.g., as described for support 642). For someapplications (not shown), the struts that form lower annular portion 676are arranged as chevrons that repeat in a circumferential pattern (e.g.,as described for support 282). It is to be noted that the frame ofsupport 662 (e.g., the struts of its upper and lower annular portions)is typically covered with a covering (e.g., described for support 282),such that the support generally resembles support 282 (e.g., as shown inFIGS. 15A-C), mutatis mutandis.

Upstream annular portion 674 of support 662 has a flexible sector 663that is more flexible than other portions of the upstream annularportion. For example, struts 679 that form sector 663 may be moreflexible (e.g., by being thinner) than struts 675 that form otherportions of upstream annular portion 674. As shown in FIG. 19B, theimplant of which support 662 is a component is typically implanted withsector 663 oriented to an anterior side 11 of mitral valve 10. Sector663 facilitates greater conformation of upstream annular portion 674 tothe anatomy (e.g., to the atrial wall separating left atrium 6 fromaorta 3), and therefore improved sealing against the anatomy.

Support 662 is shown in FIG. 19B as being used with components ofimplant 280 (e.g., valve frame 284 and sheet 286), but it is to be notedthat the scope of the invention includes support 662 being used withcomponents of other implants.

Reference is made to FIGS. 20A-C, which are schematic illustrations ofan implant 380 comprising a support frame 382, a prosthetic valve frame384, and a flexible sheet 386 coupling the support frame to theprosthetic valve frame, in accordance with some applications of theinvention.

Valve frame 384 may be identical, mutatis mutandis, to another valveframe described herein, such as valve frame 264 or valve frame 284. Aplurality of snares 388 protrude radially outward and upstream fromvalve frame 384, typically from a downstream portion of the valve frame.Snares 388 may be coupled rigidly to valve frame 384 (e.g., as shown) ormay be coupled in another fashion, such as via a flexible sheet, asdescribed for implant 280, mutatis mutandis. Snares 388 may be identicalto other snares described herein, mutatis mutandis.

A valve member (e.g., a plurality of prosthetic leaflets) is disposedwithin the lumen defined by valve frame 384, so as to facilitate one-waydownstream movement of blood through the lumen, e.g., as describedherein for other valve members. For clarity, the valve member is notshown in FIGS. 20A-C.

Implant 380 has a compressed state for percutaneous (e.g., transluminal)delivery to the heart, and is intracorporeally expandable into anexpanded state. In the compressed state of implant 380, frames 382 and384 are in respective compressed states thereof. FIGS. 20A-C showimplant 380 in its expanded state, with frames 382 and 384 in respectiveexpanded states thereof, and the descriptions herein refer to implant380 in its expanded state, unless stated otherwise.

FIG. 20A shows support frame 382 and valve frame 384, with the supportframe in a relaxed state. FIG. 20B shows implant 380 with support frame382 in its relaxed state, and FIG. 20C shows the implant with thesupport frame in a constrained state thereof. The relaxed andconstrained states of implant 380 (and of support frame 382) aredescribed in more detail hereinbelow.

Support frame 382 has a generally toroid shape, defining an opening 390through the support frame, and dimensioned to be placed against anupstream surface of the native heart valve such that the support framecircumscribes the valve orifice. Typically, support frame 382 isdimensioned to be placed on the annulus of the native valve. It is to benoted that the term toroid (including the specification and the claims)is describable as the result of revolving a plane geometric figure abouta central longitudinal axis. The generally toroid shape of support frame382 is describable as the result of revolving a plane geometric figureabout a central longitudinal axis ax3 of the support frame (and/or ofimplant 380 as a whole). That is, an axis of revolution ax4 of thetoroid shape circumscribes axis ax3, and the toroid shape is describableas the result of moving the plane geometric figure along the axis ofrevolution. It is to be noted that the position of axis of revolutionax4 is merely an illustrative example, and may pass through another partof the plane geometric figure.

For some applications, and as shown, the plane geometric figure isU-shaped or V-shaped (e.g., as shown in the cross-sections of FIGS.20B-C). However, the plane geometric figure may alternatively oradditionally have a different shape.

FIG. 20B shows implant 380 in its relaxed state (e.g., in a relaxedstate of support frame 382).

Valve frame 384 is held by sheet 386 at a given height with respect tosupport frame 382. For some applications, and as shown, in the relaxedstate of implant 380, at least part of the lumen defined by valve frame384 is disposed within opening 390 of the support frame.

When valve frame 384 is moved in a downstream direction, a force isapplied to support frame 382 via sheet 386, and the support frame 382responsively rolls inward (e.g., about axis of revolution ax4) such thatan orientation of the plane geometric figure with respect to opening 390changes (e.g., the plane geometric figure deflects and/or rotates). Forexample, in FIG. 20B the U-shape is oriented such that the arms of theU-shape point at right angles to opening 390, whereas in FIG. 20C, thearms point more toward the opening.

Support frame 382 is biased to assume its relaxed state, such thatremoval of the force (e.g., releasing of valve frame 384) results inimplant 380 returning to the state shown in FIG. 20B. Duringimplantation at the native valve (e.g., using techniques similar tothose described elsewhere herein) such that snares 388 are disposeddownstream of the native valve and support frame 382 is disposedupstream of the native valve, the force is applied such that implant 380is in its constrained state.

When the force is removed, the implant moves toward its relaxed state,thereby sandwiching tissue of the native valve between snares 388 andsupport frame 382. For some applications, and as shown, in theconstrained state, at least part of the lumen defined by valve frame 384is disposed within opening 390 of the support frame. Alternatively, thelumen defined by the valve frame may be disposed entirely downstream ofopening 390.

For some applications support frame 382 defines an inner ring 394 and anouter ring 396, each ring defined by a circumferential arrangement ofcells, each cell of the inner ring coupled to adjacent cells of theinner ring, and to a corresponding cell of the outer ring. The innerring defines one arm of the U-shape, the outer ring defines the otherarm of the U-shape, and the inner ring cells are coupled to the outerring cells at a trough 398 of the U-shape. The rolling of frame 382 inresponse to the applied force compresses the inner ring cells and outerring cells, at least in part, i.e., reducing a width d17 of the innerring cells and a width d18 of the outer ring cells. Upon removal of theforce, the cells re-widen, thereby causing support frame 382 to rollback toward its relaxed state.

The mechanics described in the above paragraph may be alternativelydescribed as follows: The rolling of the frame moves at least part ofinner ring 394 and at least part of outer ring 396 radially inward, suchthat a diameter of each ring becomes smaller. Upon removal of the forceeach ring re-expands toward its original diameter, thereby causingsupport frame 382 to roll back toward its relaxed state. That is,support frame 382 defines at least one ring that is compressed as theframe rolls inward, and expands as the frame rolls outward. This isillustrated in the cross-sections of FIGS. 20B-C. A diameter of innerring 394, measured at the point of coupling between cells of the innerring, is greater when support frame 382 is in its relaxed state(diameter d22 of FIG. 20B) than when the support frame is in itsconstrained state (diameter d23 of FIG. 20C).

The biasing of support frame 382 to assume its relaxed state istypically achieved by forming the support frame from a shape-memorymaterial such as Nitinol.

For some applications, and as shown, sheet 386 extends over the lip ofinner ring 394, and covers at least part of the inner ring. For somesuch applications, sheet 386 is circumferentially attached to supportframe 382 at least at trough 398.

The rolling inward of support frame 382 typically involves amost-radially-inward point of contact between the support frame andsheet 386 moving in a downstream direction, and further typicallyinvolves the most-radially-inward point of contact moving radiallyinward. For example, and as shown in the cross-sections of FIGS. 20B-C,for some applications the most-radially-inward point of contact betweensupport frame 382 and sheet 386 is the lip of inner ring 394, and therolling inwards involves the lip of the inner ring moving in adownstream and radially-inward direction.

Reference is made to FIGS. 21A-C, which are schematic illustrations of asystem 400 for stretching an elastic coupling between frames of animplant, in accordance with some applications of the invention. For someapplications, an implant 402 comprises a first frame 404 elasticallycoupled to a second frame 408. For some such applications, implant 402comprises a flexible sheet 406 that extends between frame 404 and frame408, and provides fluid sealing and/or fluid communication between theframes once the implant is implanted. The elastic coupling may beprovided by the flexible sheet, and/or may be provided by anothermechanism. The elastic coupling typically facilitates sandwiching oftissue of a subject between the two frames upon implantation of theimplant. Moving frames 404 and 408 away from each other (therebystretching the elastic coupling between the frames) prior toimplantation facilitates positioning of the frames (or parts thereof) oneither side of the tissue, such that upon release of the stretchingforce, the elastic coupling draws the frames closer together, therebysandwiching the tissue between the frames (or parts thereof).

FIGS. 21A-C are general schematic illustrations. Implant 402 maycomprise any of the implants described herein in which a flexible sheetcouples two frames, or implant 402 may comprise another implant. Forexample, implant 402 may comprise implant 20, implant 80, implant 100,implant 120, implant 140, implant 160, implant 180, implant 200, implant240, implant 260, or implant 380, mutatis mutandis.

Prior to implantation, implant 402 is coupled to a delivery tool 410,which typically comprises a central rod (e.g., as described elsewhereherein, mulatis mutandis). For some applications, implant 402 isprovided pre-coupled to the delivery tool (e.g., by being compressed, or“crimped”, onto the delivery tool, as is known in the art, mutatismutandis). For some applications, part or all of implant 402 is coupledto delivery tool 410 soon before implantation (e.g., by the operatingphysician, or by a technician at the operating institution). Forexample, for applications in which one of the frames (e.g., frame 408)comprises a prosthetic valve frame that comprises prosthetic leaflets,it may be desirable that the prosthetic valve frame not remaincompressed for an extended period, and so at least that frame iscompressed against the delivery tool soon before implantation. FIG. 21Ashows implant 402 after both frame 404 and frame 408 have been coupledto tool 410, and are in tandem with each other.

Once frames 404 and 408 are coupled to the delivery tool (e.g., torespective connectors of the delivery tool), the elastic couplingbetween the frames is stretched by increasing a distance between theframes, such as by increasing a distance between the connectors to whichthe frames are coupled (FIG. 21B). For example, and as shown, tool 410may comprise a first portion 412 (which may comprise a first connector,not shown) and a second portion 414 (which may comprise a secondconnector, not shown), and movement of portion 414 axially with respectto portion 412 (e.g., increasing an overall length of tool 410).

FIG. 21C shows implant 402 being advanced into a delivery tube 416(e.g., a catheter) subsequently to the above-described stretching.However it is to be noted that the scope of the invention includesperforming the stretching after the implant has been advanced intodelivery tube 416 (e.g., while the implant is in a vicinity of theimplantation site).

Reference is now made to FIGS. 22, 23, 24A-C, and 25A-K, which areschematic illustrations of an implant 460, and a system 500 comprisingimplant 460 and a delivery tool 502, in accordance with someapplications of the invention. Implant 460 is similar, and comprisessimilar elements, to other implants described hereinabove. In particularimplant 460 is typically identical to implant 260, except where noted,and components of implant 460 share similar structure and/or functionwith identically-named elements of implant 260, except where noted.

Implant 460 comprises an upstream frame 462, a downstream frame 464, andat least one flexible sheet 466 that couples the upstream frame to thedownstream frame. Typically, implant 460 comprises two flexible sheets466, such as a flexible sheet 466 a and a flexible sheet 466 b, whicheach couple upstream frame 462 to downstream frame 464. Downstream frame464 comprises a tubular body that defines a lumen therethrough (e.g., asdescribed hereinabove for other downstream frames), and a plurality ofsnares 468. As shown, snares 468 typically meet the valve body definedby frame 464 toward a downstream end of the valve body, and do notextend in an upstream direction as far as the upstream end of frame 464.Implant 460 comprises a valve member (e.g., a plurality of prostheticleaflets) 50 disposed within the lumen defined by downstream frame 464,e.g., as described hereinabove, mutatis mutandis.

As described for upstream frame 22, mutatis mutandis, upstream frame 462(and other upstream frames described herein, such as upstream frame 262)may be considered to define an upstream opening 150 (i.e., an openingdefined by an upstream end of the upstream frame) and a downstreamopening 150′ (i.e., an opening defined by a downstream end of theupstream frame). An upstream end 492 of frame 462 defines upstreamopening 150 of frame 462, and a downstream end 494 of frame 462 definesdownstream opening 150′ of frame 462. It is to be noted that throughoutthis application (including the specification and the claims), in theabsence of further definition, the “opening” of any of the upstreamframes typically refers to the downstream opening of the upstream frame.

FIG. 22 shows implant 460 in its expanded state, in which an upstreamportion (e.g., an upstream end) of downstream frame 464 is disposedlongitudinally upstream of opening 150′ of upstream frame 462 (e.g., asdescribed for implant 260, mulatis mutandis). That is, implant 460 has acentral longitudinal axis, and the upstream portion of downstream frame464 is disposed further upstream along the longitudinal axis than isopening 150′. The position of frames 464 with respect to frame 462 isdue to the nature of coupling of the frames to each other via sheet(s)466. As described hereinbelow, implant 460 is transluminally deliveredin a compressed state in which frames 462 and 464 are both compressed,and are disposed in tandem. At the implantation site, expansion ofupstream frame 462 toward its expanded state pulls valve frame 464longitudinally into frame 462 (i.e., into opening 150′) by pulling sheet466 a and/or sheet 466 b radially outward (i.e., tensioning thesheet(s)).

As described for implant 260, mutatis mutandis, in the expanded state ofimplant 460, a diameter of frame 464 is smaller than a diameter ofopening 150′ defined by downstream end 494 of frame 462. Sheet 466 aextends radially inward from frame 462 to frame 464, and iscircumferentially attached to frame 464 at a first longitudinal site 474a of frame 464. For some applications, sheet 466 a is identical to sheet266 a described hereinabove, mutatis mutandis. Sheet 466 b also extendsradially inward from frame 462, and is circumferentially attached toframe 464 at a second longitudinal site 474 b of frame 464.

Typically, longitudinal site 474 b is closer to upstream portion 42 thanis longitudinal site 474 b. For example, longitudinal site 474 b may beat least 4 mm and/or less than 10 mm closer to an upstream end of frame464 than is longitudinal site 474 b (e.g., 4-10 mm closer, or at least 3mm closer, such as 3-10 mm closer, e.g., about 6 mm closer). For someapplications, longitudinal site 474 b is at the upstream end of frame464, although is shown in FIG. 22 as slightly downstream of this.

Typically, sheet 466 b is attached to upstream frame 462 furtherupstream than is sheet 466 a.

For example, and as shown, sheet 466 a may be attached to (i.e., mayextend from) downstream end 494 of frame 462, whereas sheet 466 b may beattached to (i.e., may extend from) upstream end 492 of frame 462. Thesites of attachment of sheets 466 to frames 462 and 464 (i) facilitatesthe longitudinal pulling of frame 464 into frame 462 (e.g., via opening150′) by the radial expansion of frame 462, (ii) facilitate smoothbloodflow from opening 150 into the lumen of downstream frame 464,and/or (iii) defines, between sheets 466 a and 466 b, a chamber 476(e.g., a closed chamber) that circumscribes frame 464. Chamber 476 istypically toroidal. Subsequently to implantation of implant 460, tissueformation typically occurs within chamber 476, e.g., due to bloodentering the chamber 476 by passing through the flexible sheets (e.g.,at least one of the sheets is at least partially blood-permeable). Forsome applications this tissue formation is hypothesized to graduallyincrease rigidity of implant 460.

Therefore, as described with reference to implants 260 and 460,percutaneously-implantable apparatus is provided, comprising (i) a firstframe; (ii) a second frame; and (iii) a plurality of flexible sheetscomprising at least a first flexible sheet and a second flexible sheet,at least the first sheet coupling the first frame to the second frame,and the plurality of flexible sheets being coupled to the first frameand the second frame such that a closed chamber is disposed between thefirst sheet and the second sheet, and at least one of the sheets beingat least partially blood-permeable.

As described hereinabove for other implants, mulatis mutandis, frames462 and 464 (or at least portions thereof) are typically covered and/orlined, and flexible sheets 466 a and 466 b may extend over portions ofthe frames so as to perform this function. For example, and as shown,sheet 466 a typically extends from longitudinal site 474 a of frame 464,to downstream end 494 of frame 462, and over an outer surface of frame462. Sheet 466 a may continue to extend around upstream end 492 of frame462 and line part of an inner surface of frame 462, as shown. Frame 464is typically at least partly lined, e.g., with a fabric, which may bethe same material as sheet(s) 466. For some applications, and as shown,frame 464 has unlined zones, e.g., positioned where leaflets 50 deflectoutward to allow fluid flow.

FIG. 23 shows system 500, including several sub-views, with implant 460,in a compressed delivery state, loaded onto delivery tool 502, inaccordance with some applications of the invention.

Delivery tool 502 comprises one or more steerable catheters, such as afirst catheter 504 (having a distal steerable portion 505) and a secondcatheter 506, which extends through catheter 504 such that a steerabledistal portion 507 of catheter 506 is disposed out of the distal end ofcatheter 504. Catheter 504 has an external diameter d24 that istypically 7-10 mm (e.g., 8-9 mm), and catheter 506 has an externaldiameter d25 that is typically 5-8 mm (e.g., 6-7 mm), and is smallerthan an internal diameter of catheter 504. Tool 502 further comprises arod 508 (e.g., a central rod), which has an external diameter d27 thatis smaller than an internal diameter of catheter 506. Rod 508 extendsthrough catheter 506 such that a steerable distal portion 509 of rod 508is disposed out of the distal end of catheter 506. For someapplications, a width (e.g., a greatest width) d27 of implant 460 in itscompressed state is greater than the internal diameter of catheter 504.This is possible because, as described hereinbelow, implant 460 is notadvanced through catheters 504 and 506, but instead is advanced with thecatheters, while disposed distally to them. Typically, catheter 504,catheter 506 and rod 508 each comprise a polymer. The arrangement ofcatheter 504, catheter 506 and rod 508 is most clearly shown in sub-viewD.

There is therefore provided, in accordance with some applications of theinvention, apparatus comprising: (i) a first catheter (e.g., catheter504), dimensioned for transfemoral and transseptal advancement into aleft atrium of a heart of a subject, and having a lumen that has aninternal diameter; (ii) a second catheter (e.g., catheter 506), havingan external diameter that is smaller than the internal diameter, thesecond catheter being sufficiently long to extend through the firstcatheter such that a steerable distal portion (e.g., portion 507) of thesecond catheter extends out of a distal end of the first catheter, and(iii) an implant (e.g., implant 460), having a compressed state in whichthe implant is transfemorally and transseptally advanceable into theleft atrium by the first catheter and the second catheter, and in whicha width of the implant is greater than the internal diameter of thefirst catheter.

It is to be noted that the term “steerable” (including the specificationand the claims) means actively steerable, e.g., by using anextracorporeal controller to effect bending. (This is in contrast to aflexible but non-steerable element, which may bend in response toencountering forces during advancement through the body of the subject.)Bending of portion 505 of catheter 504 is performed by actuating acontroller 565 (e.g., on a handle 555 at a proximal end of catheter 504)that is operably coupled (e.g., via pull-wires) to portion 505. Bendingof portion 507 of catheter 506 is performed by actuating a controller567 (e.g., on a handle 557 at a proximal end of catheter 506) that isoperably coupled (e.g., via pull-wires) to portion 507. Bending ofportion 509 of rod 508 is performed by actuating a controller 569 (e.g.,on a handle 559 at a proximal end of rod 508) that is operably coupled(e.g., via pull-wires) to portion 509. Typically, a bending plane ofportion 507 is orthogonal to a bending plane of portion 505. Therebytogether catheters 504 and 506 provide movement in two dimensions.Portion 509 of rod 508 may be steerable on one or more bending planes(e.g., on two bending planes). As well as being steerable, rod 508 istypically slidable longitudinally with respect to the catheters (e.g.,by sliding handle 559, such as along a track 558).

As shown in sub-views C and B, implant 460, in its compressed state, isdisposed around steerable distal portion 509 of rod 508, with frames 464and 462 in tandem with each other. Sub-view C shows implant 460including sheets 466 (which also serve as coverings for the frames ofimplant 460, e.g., as described elsewhere hereinabove, mulatismutandis), and sub-view B shows the implant in the absence of sheets466, thereby more clearly showing the positions of frames 462 and 464.Frame 462 is disposed around rod 508 (e.g., around distal portion 509thereof) at a first longitudinal site 560 a, sheet 466 is disposedaround rod 508 at a second longitudinal site 560 b, and frame 464 isdisposed around rod 508 at a third longitudinal site 560 c. Distalportion 509 is bendable at least at second longitudinal site 560 b,which serves as an articulation zone.

As shown in sub-view A (as well as the primary view), a sheath 510 isdisposed over at least implant 460 (and typically over at least portions507 and 509 of catheters 506 and 508). Sheath 510 is thin (e.g., greaterthan 100 microns and/or less than 300 microns, e.g., 100-300 microns,such as about 200 microns thick), typically has insignificantcompressive, torsional, or deflective strength, and is sufficientlyflexible to passively bend in response to the bending of rod 508 and thearticulation between frames 462 and 464. Sheath 510 comprises alow-friction material (e.g., is formed from the low-friction material,or is coated in the low-friction material) such aspolytetrafluoroethylene (PTFE).

FIGS. 24A-C show transverse cross-sections through system 500 (i.e.,cross-sections transverse to a longitudinal axis of system 500), thelocation of each cross-section being indicated in sub-view A of FIG. 23.Each of the cross-sections shows concentric layers. A firstcross-section (FIG. 24A) shows concentric layers comprising,respectively, from inside outwardly: polymer (of rod 508), fabric (ofsheet 466 b), metal (of frame 462), and PTFE (of sheath 510). Typically,another layer of fabric (the covering of frame 462, typically part ofsheet 466 a) is disposed between the metal and PTFE layers.

A second cross-section (FIG. 24B) shows concentric layers comprising,respectively, from inside outwardly: polymer (of rod 508), fabric (ofsheet(s) 466), and PTFE (of sheath 510), without a metal layer betweenthe polymer and the fabric, or between the fabric and the PTFE.Typically, and as shown, there are also no struts (e.g., struts of aframe) between the polymer and the fabric, or between the fabric and thePTFE. Typically, and as shown, there is no metal at all between thepolymer and the fabric, or between the fabric and the PTFE.

A third cross-section (FIG. 24C) shows concentric layers comprising,respectively, from inside outwardly: polymer (of rod 508), pericardialtissue (of leaflets 50), metal (of frame 464), and PTFE (of sheath 510).Typically, another layer 470 of fabric (which lines the lumen of frame464) is disposed between the pericardial tissue layer and the metallayer. The second cross-section is disposed longitudinally between thefirst and third cross-sections.

It is to be noted that in this context, the term “layer” (including inthe specification and in the claims) may refer to a continuous layer(such as that defined by sheath 510) or an interrupted layer (such asthat which might defined by the struts of frames 462 and 464, whenviewed in cross-section).

FIGS. 25A-K show system 500 in use, with delivery tool 502 being used toimplant implant 460, in accordance with some applications of theinvention. The femoral vein 16 is punctured (e.g., using the Seldingertechnique), and a guidewire 520 is transfemorally and transseptallyadvanced to the left side of the heart of the subject (at least intoleft atrium 6, and typically into left ventricle 8).

A trocar 522 (e.g., a standard, commercially-available trocar) is usedto provide access to the femoral vein. A distal portion of system 500(comprising implant 460, and distal portions of catheter 504, catheter506, rod 508 and sheath 510) is advanced through trocar 522 into femoralvein 16, along inferior vena cava 17, into right atrium 7 (FIG. 25A).For some applications (and as shown), system 500 is advanced alongguidewire 520. Alternatively, guidewire 520 is used to facilitate septalpuncture, and is removed prior to advancing system 500.

It is to be noted that no guide catheter is advanced to the heart priorto advancing implant 460.

Rather, system 500 is advanced as-is, through the vasculature. Rather,sheath 510 slides through the vasculature simultaneously with implant460, and reduces friction between implant 460 and the vasculature.

It is to be further noted, that implant 460 is not disposed within asteerable (i.e., actively bendable) catheter for any part of theimplantation process. Rather, and as can be understood from FIG. 23, andFIGS. 25A-K, implant 460 is disposed distally to steerable catheters 504and 508.

System 500 is advanced transseptally into left atrium 6 (FIG. 25B). Asshown, the steerability of catheters 504 and 508, and of rod 508,facilitates this. Furthermore, the steerability of rod 508 facilitatesarticulation of implant 460 down toward mitral valve 10, immediatelyafter the implant clears the interatrial septum (or even before implant460 has completely traversed the septum). It is hypothesized that, interalia, (i) the articulatable coupling between frames 462 and 464 providedby sheet(s) 466, and (ii) the exploitation of this articulation bysteerable rod 508, facilitates transfemoral and transseptalimplantation, at the mitral valve, of an implant having a greater length(in its compressed state) than would be possible for a non-articulatableimplant, or using a delivery system that does not actively articulatethe implant during delivery.

System 500 is then advanced between leaflets 12 of mitral valve 10,typically such that (within sheath 510) at least part of frame 464 isdisposed in left ventricle 8, and at least part of frame 462 is disposedwithin left atrium 6 (FIG. 25C). For some applications, the transitionbetween the stage shown in FIG. 25B and that shown in 25C involves (i)advancing system 500 distally, (ii) increasing bending of catheter 504and/or of catheter 506, and (iii) reducing the bending of rod 508 (andtherefore the articulation of implant 460).

There is therefore provided, in accordance with some applications of theinvention, a method comprising (i) using a delivery tool, percutaneouslyadvancing toward a heart of a subject a prosthetic valve implant coupledto a distal portion of the delivery tool, the implant comprising a firstframe coupled to a second frame; (ii) subsequently, articulating thefirst frame with respect to the second frame by bending the distalportion of the delivery tool; (iii) subsequently, reducing thearticulation of the first frame with respect to the second frame byreducing the bending of the distal portion of the delivery tool; and(iv) subsequently, implanting the implant in the heart of the subject.For some applications, between the step of articulating the first frameand the step of implanting, another portion of the delivery tool,proximal to the distal portion, is bent.

There is therefore also provided, in accordance with some applicationsof the invention, apparatus, comprising: (i) a delivery tool (e.g., tool502) comprising: (a) a first catheter (e.g., catheter 504), (b) a secondcatheter (e.g., catheter 506) extending through the first catheter, and(c) one or more extracorporeal controllers (e.g., controllers 565, 567,and 569), coupled to a proximal end of at least one of the firstcatheter and the second catheter; and (ii) an implant (e.g., implant460), comprising a first frame (e.g., frame 462) articulatably coupledto a second frame (e.g., frame 464), and coupled to a distal portion ofthe delivery tool, distal to a distal end of the first catheter and to adistal end of the second catheter, and the one or more extracorporealcontrollers are actuatable to transition the apparatus between: (i) afirst state in which the first catheter and the second catheter arestraight, and the first frame is articulated with respect to the secondframe, and (ii) a second state in which a distal portion of at least oneof the first catheter and the second catheter is bent, and the firstframe is collinear with the second frame.

Subsequently, implant 460 is unsheathed (FIGS. 25D-E). A distal portionof sheath 510 is typically reversibly secured to a distal portion of rod508. For example, and as shown, rod 508 may have a bulbous distal end512 with a circumferential groove 514, and a loop of a wire 516 maysecure the distal portion of the sheath within the groove. Theunsheathing is performed using an extracorporeal controller 518. Anexample of such a controller is shown. Controller 518 has a tab 517which is attached to wire 516. Sheath 510 is released from distal end512 by pulling tab 517, which disengages wire 516 from groove 514 (FIG.25D). Controller 518 is attached to a proximal portion of sheath 510,and sliding of the controller proximally (e.g., with respect to catheter504) draws sheath 510 proximally, thereby unsheathing implant 460 (FIG.25E). For some applications, controller 518 comprises a lock 519 (e.g.,comprising a set screw), which, while locked, prevents movement ofsheath 510 (e.g., by gripping an outer surface of catheter 504).

As shown in FIG. 25E, despite the unsheathing of implant 460, theimplant remains in its compressed state. A plurality of restraints 530restrain the implant in its compressed state. Typically, restraints 530are coupled to, and actuated via, rod 508. Typically, a first restraint530 a restrains snares 468, a second restraint 530 b restrainsdownstream frame 464 (e.g., the valve body thereof), and a thirdrestraint 530 c restrains upstream frame 462. Further typically,restraints 530 are disengaged using one or more extracorporeal restraintcontrollers 532 (e.g., respective controllers 532 a, 532 b, and 532 c),such as switches, on handle 559. For some applications, and as shown,each restraint 530 comprises a respective loop of wire, whichcircumscribes a respective portion of implant 460 (most clearly shown inFIG. 23 sub-view B). However, restraints 530 may comprise another typeof restraint, such as a latch or detent that protrudes radially from rod508.

First restraint 530 a, which restrains snares 468 in their compressedstate, is disengaged, thereby allowing the snares to extend radiallyaway from frame 464 (e.g., from the valve body thereof) (FIG. 25F).Snares 468 are shown in the figures as (i) being disposed against thevalve body defined by frame 464 when in their compressed state, and (ii)moving through an acute angle when released. However, snares 468 mayhave a different configuration, such as (i) being disposeddistal/downstream to the valve body defined by frame 464 when in theircompressed state, and (ii) moving through an obtuse angle when released.

Second restraint 530 b remains in place, restraining frame 464 (e.g.,the valve body thereof) in its compressed state, and third restraint 530c remains in place, restraining frame 462 in its compressed state.Typically, at this stage, one or more imaging techniques (e.g.,fluoroscopy) are used to determine, and optionally adjust, the positionof implant 460, and in particular of snares 468 thereof.

FIG. 25G illustrates the use of an imaging machine (e.g., a fluoroscope)to provide an image on a display 540, while the position of implant 460is adjusted. Once the desired position is achieved, restraint 530 b isdisengaged (e.g., using restraint controller 532 b), thereby allowingdownstream frame 464 to expand toward its expanded state (FIG. 25H).

There is therefore provided (e.g., as described with reference to FIGS.25A-H) a method, comprising (i) transluminally advancing an implant to aheart of a subject while the implant is disposed within a sheath, theimplant including (a) an expandable valve frame in a compressed state,(b) a valve member disposed within the valve frame, and (c) a pluralityof snares coupled to the valve frame; (ii) subsequently, entirelyunsheathing the valve frame and the snares from the sheath; (iii)subsequently (i.e., not instantaneously), extending the snares radiallyoutward from the valve frame while retaining the valve frame in thecompressed state; and (iv) subsequently, expanding the valve frameradially outward.

As shown in FIG. 25H, upstream frame 462 continues to be restrained inits compressed state by restraint 530 c. For some applications, thedimension of sheet(s) 466 are such that, while frame 462 remains in itscompressed state, the upstream frame limits expansion of the upstreamportion of frame 464 via tension on the sheet(s). Expansion of theupstream portion of frame 464 is typically limited more than isexpansion of a downstream portion of frame 464. Typically, in such astate, frame 464 (e.g., the valve body thereof) and/or sheet(s) 466 arefrustoconical. For example, and as shown, sheet 466 a may define a firstconical frustum, and frame 464 may form a second conical frustum, e.g.,with steeper sides than the first conical frustum.

There is therefore provided, in accordance with some applications of theinvention, a method, comprising: (i) transluminally advancing an implantto a heart of a subject, the implant including (a) a valve frame at adownstream portion of the implant, (b) a valve member disposed withinthe valve frame, (c) a flexible sheet, and (d) a support frame at anupstream portion of the implant, coupled to the valve frame via theflexible sheet, wherein the valve frame and the support frame areconstrained in respective compressed states during the advancing; and(ii) within the heart, (a) releasing the valve frame such that the valveframe automatically expands from its compressed state, while (b)maintaining the support frame in its compressed state such that thesupport frame limits expansion of an upstream portion of the valve framevia tension on the sheet.

Tissue of the native valve (e.g., leaflet tissue) is engaged usingsnares 468 by moving implant 460 upstream (e.g., by withdrawing rod 508into catheter 506) (FIG. 25I). This also moves frame 462 into (orfurther into) atrium 6. This step is typically performed after the stepshown in FIG. 25H, but may alternatively be performed before the stepshown in FIG. 25H.

Subsequently, restraint 530 c is disengaged (e.g., using restraintcontroller 532 c), thereby allowing upstream frame 462 to expand towardits expanded state (FIG. 25J). As described hereinabove, the radialexpansion of frame 462 pulls sheet(s) 466 radially outward, such thatframe 464 is pulled into frame 462, and snares 468 become closer toframe 462. It is to be noted that this description relates to therelative movement between frames 462 and 464, independent of theirposition with respect to the anatomy. Therefore, although frame 464 mayremain stationary with respect to the anatomy while frame 462 expands,the effect on the implant is the same—frame 464 is pulled into frame462. The movement of snares 468 closer to frame 462 sandwiches tissue ofthe native valve (e.g., leaflets 12), thereby securing implant 460 atthe native valve, e.g., as described hereinabove, mutatis mutandis.

Subsequently, delivery tool 502 is withdrawn from the subject, leavingimplant 460 implanted at the native valve, and serving as a prostheticvalve (FIG. 25K).

There is therefore provided, in accordance with some applications of theinvention, a method comprising (i) transfemorally advancing to the hearta rod (e.g., rod 508) and an implant (e.g., implant 460) compressedaround a distal portion of the rod, the implant including a first frame(e.g., frame 462), a second frame (e.g., frame 464), a valve member(e.g., leaflets 50) disposed within the second frame, and a flexiblesheet (e.g., sheet 466 a) coupling the first frame to the second frame,wherein the first frame and the second frame are in tandem; (ii)subsequently, articulating the second frame with respect to the firstframe by bending the distal portion of the rod by operating anextracorporeal controller (e.g., controller 569); and (iii)subsequently, implanting the implant at the valve such that at leastpart of the first frame is disposed on a first side of the valve and atleast part of the second frame is disposed on a second side of thevalve.

As described for implant 460, and for other implants, there is alsoprovided, in accordance with some applications of the invention, amethod, comprising (i) percutaneously delivering into the body animplant in a compressed state, the implant (a) having a longitudinalaxis, and (b) including a first frame, a flexible sheet, and a secondframe coupled, via the flexible sheet, to the first frame in tandemalong the longitudinal axis; and (ii) subsequently, radially expandingthe first frame such that the first frame pulls the second framelongitudinally into the first frame by pulling the sheet radiallyoutward.

There is also provided, in accordance with some applications of theinvention, apparatus comprising (i) a first frame having a compressedstate in which the frame is transluminally advanceable into the subject,and having a tendency to radially expand from the compressed statetoward an expanded state; and (ii) a second frame distinct from thefirst frame, and coupled to the first frame in tandem with the firstframe along a longitudinal axis of the implant, and the coupling of thesecond frame to the first frame is such that a radially outward force ofthe first frame during its expansion is converted into a longitudinalforce that pulls the second frame into the first frame.

Although transfemoral and transseptal delivery is described, for someapplications a retrograde approach (i.e., via the aortic valve) is used,mulatis mutandis. For such applications, as well as other differences,implant 460 is disposed on delivery tool 502 in the inverse orientation(i.e., with frame 464 disposed proximally to frame 462).

It is to be noted that delivery tool 502 may be used to deliverprosthetic heart valves other than implant 460. For some applications,tool 502 is used to deliver a prosthetic valve that, in its deliverystate, does not have an articulation zone between two frames. For someapplications, tool 502 is used to deliver a prosthetic valve that, inits delivery state, is rigid. For such applications, rod 508 istypically used to orient the compressed prosthetic valve with respect tothe native valve.

Reference is again made to FIGS. 8, 13A-C, 14A-C, 20A-C, 22, and 25A-K.It is to be noted that, for some applications, implants described hereinare implanted such that at least part of the valve frame (e.g., at leastpart of the lumen defined by the valve frame) is disposed within theopening defined by the support frame, without placing the valve frame(or at least not the tubular body thereof) in contact with the supportframe. For such applications, the valve frame typically does not apply aradially-expansive force to the support frame. For some suchapplications, the valve frame (e.g., the tubular body thereof) has adiameter that is less than 80 percent as great (e.g., 50-80 percent),such as less than 75 percent (e.g., 50-75 percent, such as 60-75percent) as the diameter of the opening of the support frame. For somesuch applications, during delivery, the valve frame and the supportframe are arranged collinearly, e.g., with the flexible sheet providingan articulation zone therebetween, e.g., as described with reference toFIG. 17, mutatis mutandis.

Therefore apparatus is provided, in accordance with some applications ofthe invention, comprising (i) a support frame, having a compressedstate, and an expanded state in which the support frame defines anopening therethrough, and is dimensioned to be placed against anupstream surface of the native valve such that the opening is disposedover an orifice defined by the native valve; (ii) a flexible sheet; and(i) a valve frame that (a) has a compressed state, and an expanded statein which the valve frame defines a lumen therethrough, (b) comprises avalve member disposed within the lumen, and (c) is coupled to thesupport frame via the flexible sheet such that when the support frame isin its expanded state, and the valve frame is in its expanded state, atleast part of the lumen is disposed within the opening, and the valveframe is not in contact with the support frame.

Reference is again made to FIGS. 14A-C and 22. As described hereinabove,both implant 260 and implant 460 define a closed toroidal chamber (276,476), defined by the flexible sheets that couple the frames of theimplant. On at least one surface of the chamber the fabric does notcontact either of the frames. There is therefore provided, in accordancewith some applications of the invention, a percutaneously-implantableimplant, comprising (i) a metallic frame; and (ii) a closed chamber (a)having a toroid shape, and (b) defined by a fabric that is at leastpartially blood-permeable, and is coupled to the metallic frame. Thetoroid shape is describable as a result of revolving, about an axis, across-section of the chamber in which (a) the chamber is delimited by aboundary of the fabric (for both implant 260 and implant 460 theboundary is shown roughly as an irregular quadrilateral), and (b) atleast a portion of the boundary does not contact the metallic frame(e.g., the portions where the flexible sheets extend from one of theframes to the other one of the frames). For some applications, at atleast one position of the revolution, at least part of the boundarycontacts the metallic frame (e.g., the part of the boundary where aframe is covered in the fabric that defines the chamber). For someapplications, at every position of the revolution, at least part of theboundary contacts the metallic frame.

Reference is again made to FIGS. 1A-25K. Throughout the presentapplication, including the specification and the claims, frames aredescribed as being coupled to each other “by a flexible sheet” or “via aflexible sheet”. It is to be noted that, in this context, the couplingis primarily provided by the flexible sheet. That is, the frames areprimarily mechanically coupled via the sheet. For example, if otherelements were to extend between the two frames, but were to provideminor mechanical coupling (e.g., minor restriction of movement of theframes relative to each other), the frames should still be understood asbeing coupled by/via the flexible sheet. In contrast, where otherelements provide the primary coupling, and a flexible sheet also extendsbetween the two frames (e.g., merely to provide sealed fluidcommunication), the frames should not be understood as being coupledby/via the flexible sheet.

Reference is again made to FIGS. 1A-25K. Typically, the implantsdescribed herein are provided (e.g., in a sealed product container) withtheir downstream frame/valve frame in its expanded state to increase theshelf-life of the valve member disposed within. Typically, the implantsare provided with their upstream frame also in its expanded state.However, for some applications, the implants are provided with theirdownstream frame in its expanded state, but its upstream frames in itscompressed state. For some such applications, a method is provided, foruse with an implant that includes a first frame coupled to a secondframe, and a valve member disposed within the second frame, the methodcomprising (i) while the second frame is coupled to the first frame,compressing the second frame into a compressed state for percutaneousadvancement into a subject; (ii) without compressing the first frame,percutaneously advancing the implant into the subject; and (iii)expanding the first frame and the second frame inside the subject. Forsome such applications, a crimping tool is provided with the implant,for compressing the second frame into its compressed state.

For some applications, the apparatus and techniques described herein maybe used in combination with apparatus and techniques described in one ormore of the following references, which are incorporated herein byreference:

-   -   US patent application publication 2013/0172992 to Gross et al.;    -   U.S. Pat. No. 8,852,272 to Gross et al.;    -   US patent application publication 2014/0324164 to Gross et al.;    -   US patent application publication 2014/0257475 to Gross et al.;    -   US patent application publication 2014/0207231 to HaCohen et        al.; and    -   PCT patent application publication 2014/115149 to Hammer et al.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. A method for use with a native valve of a heart of a subject, thenative valve being disposed between an atrium and a ventricle of theheart, and having an annulus and leaflets, the method comprising:advancing a prosthetic valve to the heart while the prosthetic valve isin a compressed state thereof, the prosthetic valve including a tubularvalve body, snares, and an upstream support; positioning the prostheticvalve within the heart such that the snares are disposed upstream of theannulus and leaflets, and expanding the snares radially outwardlyupstream of the leaflets; subsequently, moving the prosthetic valve in adownstream direction such that the snares become disposed downstream ofthe leaflets; and while the snares remain downstream of the leaflets,expanding the upstream support within the atrium and placing theupstream support against an upstream surface of the annulus.
 2. Themethod according to claim 1, wherein expanding the snares comprisesexpanding the snares while a downstream portion of the tubular valvebody remains compressed.
 3. The method according to claim 2, whereinmoving the prosthetic valve in the downstream direction comprises movingthe prosthetic valve in the downstream direction while the downstreamportion of the tubular valve body remains compressed.
 4. The methodaccording to claim 2, further comprising expanding the downstreamportion of the valve body subsequently to expanding the snares.
 5. Themethod according to claim 4, wherein expanding the downstream portion ofthe valve body subsequently to expanding the snares comprises expandingthe downstream portion of the valve body subsequently to expanding theupstream support portion within the atrium.
 6. The method according toclaim 5, wherein expanding the downstream portion of the valve bodycomprises exposing the downstream portion of the valve body from asheath such that the downstream portion of the valve body automaticallyexpands.
 7. The method according to claim 1, further comprising,subsequently to moving the prosthetic valve in the downstream direction,and prior to expanding the upstream support within the atrium, movingthe prosthetic valve back in an upstream direction such that the snaresapply an upstream force to the leaflets.
 8. The method according toclaim 7, wherein moving the prosthetic valve back in the upstreamdirection comprises placing the snares against the leaflets such thatthe snares inhibit further movement of the prosthetic valve in anupstream direction through the native valve.
 9. The method according toclaim 1, wherein expanding the snares comprises expanding the snaressuch that the snares extend further upstream than the tubular valvebody.
 10. The method according to claim 1, wherein positioning theprosthetic valve comprises identifying a position of the prostheticvalve within the heart using an imaging technique selected from thegroup consisting of: ultrasonography and fluoroscopy.
 11. The methodaccording to claim 1, wherein expanding the upstream support within theatrium comprises expanding the upstream support while the valve body isdisposed between the leaflets.
 12. The method according to claim 1,wherein expanding the snares comprises exposing the snares from a sheathsuch that the snares automatically expand.
 13. The method according toclaim 1, wherein advancing the prosthetic valve to the heart comprisestransapically advancing the prosthetic valve to the heart.
 14. Themethod according to claim 1, wherein advancing the prosthetic valve tothe heart comprises transfemorally advancing the prosthetic valve to theheart.